Systems and methods to place one or more leads in tissue to electrically stimulate nerves of passage to treat pain

ABSTRACT

Systems and methods are provided for applying electrical stimulation to a body by an electrode spaced from a target nerve of passage. It has been discovered that pain felt, or perceived to be felt, in a given region of the body can be treated by stimulating muscle close to a “nerve of passage” in a region that is superior (i.e., cranial or upstream toward the spinal column) to the region where pain is felt, such as in a case of post-amputation residual limb pain, or purportedly felt in the case of post-amputation phantom limb pain.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/338,754 filed on Jun. 4, 2021, which is a continuation of U.S. patentapplication Ser. No. 16/251,482 filed on Jan. 18, 2019, and entitled“Systems and Methods to Place One or More Leads in Tissue toElectrically Stimulate Nerves of Passage to Treat Pain,” which is acontinuation of U.S. patent application Ser. No. 15/898,889 filed onFeb. 19, 2018 and entitled “Systems and Methods to Place One or MoreLeads in Tissue to Electrically Stimulate Nerves of Passage to TreatPain,” which is a continuation of U.S. patent application Ser. No.13/605,653 filed on Sep. 6, 2012 and entitled “Systems and Methods ToPlace One or More Leads in Tissue to Electrically Stimulate Nerves ofPassage to Treat Pain,” which claims the benefit of U.S. ProvisionalPatent Application Ser. No. 61/531,462, filed 6 Sep. 2011, and entitled“Systems and Methods to Place One or More Leads in Tissue toElectrically Stimulate Nerves of Passage to Treat Pain,” which are allincorporated herein by reference in their entirety. U.S. applicationSer. No. 13/605,653 is also a continuation in part of U.S. patentapplication Ser. No. 12/653,023, filed 7 Dec. 2009, granted on Feb. 10,2015 as U.S. Pat. No. 8,954,153, and entitled “Systems and Methods ToPlace One or More Leads in Tissue to Electrically Stimulate Nerves ofPassage to Treat Pain,” which claims the benefit of U.S. ProvisionalPatent Application Ser. No. 61/201,030, filed 5 Dec. 2008, and entitled“Systems and Methods to Place One or More Leads in Tissue for ProvidingFunctional and/or Therapeutic Stimulation,” which are all incorporatedherein by reference in their entirety. U.S. application Ser. No.13/605,653 is also a continuation-in-part of U.S. patent applicationSer. No. 12/653,029, filed 7 Dec. 2009, and entitled “Systems andMethods To Place One or Functional and/or More Leads in Tissue forProviding Therapeutic Stimulation,” which claims the benefit of U.S.Provisional Patent Application Ser. No. 61/201,030, filed 5 Dec. 2008,and entitled “Systems and Methods to Place One or More Leads in Tissuefor Providing Functional and/or Therapeutic Stimulation,” which are allincorporated herein by reference in their entirety. U.S. applicationSer. No. 13/605,653 is also a continuation-in-part of U.S. patentapplication Ser. No. 13/294,875, filed 11 Nov. 2011, and entitled“Systems and Methods to Place One or More Leads in Tissue toElectrically Stimulate Nerves to Treat Pain,” which claims the benefitof U.S. Provisional Patent Application Ser. No. 61/412,685, filed 11Nov. 2010, and entitled “Systems and Methods to Place One or More Leadsin Tissue to Electrically Stimulate Nerves to Treat Pain,” which are allincorporated herein by reference in their entirety.

FIELD OF INVENTION

This invention relates to systems and methods for placing one or moreleads in tissue to electrically stimulate nerves to treat pain.

BACKGROUND OF THE INVENTION

The electrical stimulation of nerves, often afferent nerves, toindirectly affect the stability or performance of a physiological systemcan provide functional and/or therapeutic outcomes, and has been usedfor activating target nerves to provide therapeutic relief of pain.

While existing systems and methods can provide remarkable benefits toindividuals requiring therapeutic relief, many issues and the need forimprovements still remain.

Many techniques, such as non-narcotic analgesics described below, havebeen developed to treat pain, but all of them are ultimatelyinsufficient.

Psychological strategies, such as biofeedback and psychotherapy, may beused as an adjunct to other therapies but are seldom sufficient, andthere are few studies demonstrating efficacy.

Electrical stimulation systems have been used for the relief of pain,but widespread use of available systems is limited.

There exist both external and implantable devices for providingelectrical stimulation to activate nerves and/or muscles to providetherapeutic relief of pain. These “neurostimulators” are able to providetreatment and/or therapy to individual portions of the body. Theoperation of these devices typically includes the use of an electrodeplaced either on the external surface of the skin and/or a surgicallyimplanted electrode. In most cases, surface electrode (s), cuff-styleelectrode (s), paddle-style electrode(s), spinal column electrodes,and/or percutaneous lead(s) having one or more electrodes may be used todeliver electrical stimulation to the select portion of the patient'sbody.

One example of an indication where therapeutic treatment may be providedis for the treatment of pain, such as to provide a therapy to reducepain in individuals with amputated limbs. Amputation leads to chronicpain in almost all (95%) patients, regardless of how much time hadpassed since the amputation. The pain can be extremely bothersome toamputees, significantly decrease their quality of life, correlate withincreased risk of depression, and negatively affect their inter-personalrelationships and their ability to return to work. The present methodsof treatment, which are primarily medications, are unsatisfactory inreducing amputation-related pain, have unwanted side effects, offer alow success rate, and often lead to addiction.

Most amputees have two types of pain: residual limb (stump) pain andphantom pain. Approximately 72-85% of amputees have phantom pain and68-76% of amputees have residual limb (stump) pain. Both stump pain andphantom limb pain are chronic pains experienced after an amputation, andthey are easily distinguished by the perceived location of the pain.Stump pain is sensed in the portion of the limb that remains afteramputation, and phantom limb pain is perceived in the portion of thelimb that has been removed. Typically, amputee patients with severestump pain also have severe phantom limb pain, but it is recommendedthat their responses to treatment be measured independently. Stump andphantom pain can be severe and debilitating to a large proportion ofpersons with amputations, who will unfortunately often progress througha battery of management techniques and procedures without finding relieffrom their pain.

It has been estimated that 80-95% of 1.7 million persons who currentlylive with amputations, plus the additional 185,000 persons expected toundergo amputation each year in the United States, suffer or will sufferfrom stump and/or phantom pain at an annual direct cost of $1.4-2.7billion and overall associated costs of $13 billion. Severepost-amputation pain often leads to further disability, reduced qualityof life, and frequently interferes with the simple activities of dailylife more than the amputation itself, and no available therapy issufficient to manage it.

Many techniques have been developed to treat post-amputation pain, butall of them are ultimately insufficient. One review indicated that noneof the then 68 treatments available for post-amputation pain wereuniformly successful, and later reviews have found that little haschanged; there remains a large need for an effective method of treatingstump and phantom pain. Some studies report that as few as 1% ofamputees with severe phantom and stump pain receive lasting benefit fromany of the available treatments. Presently, most patients are managedwith medications, but approximately a third of amputees still reportsevere (intensity of 7-10 on a scale of 0-10) phantom and stump pain.

Non-narcotic analgesics, such as acetaminophen or non-steroidalanti-inflammatory drugs (NSAIDS), have relatively minor side effects andare commonly used for several types of pain. However, they are general,non-targeted attempts that are rarely sufficient in managing moderate tosevere chronic post-amputation pain.

The use of narcotic analgesics, such as N-methyl-D-aspartate (NDMA)antagonists, has shown only minor success with inconsistent results.Narcotics carry the risk of addiction and side effects, such as nausea,confusion, vomiting, hallucinations, drowsiness, dizziness, headache,agitation, and insomnia. Several trials of multiple narcotic agents havefailed to show statistically significant improvement in phantom pain.

Physical methods, such as adjusting a prosthesis, may be helpful toreduce post-amputation pain, but generally only if such pain is due topoor prosthetic fit. Other physical treatments, including acupuncture,massage, and percussion or heating/cooling of the stump, have fewcomplications but also have limited data to support their use and havenot been well accepted clinically.

Psychological strategies, such as biofeedback and psychotherapy, may beused as an adjunct to other therapies but are seldom sufficient, andthere are few studies demonstrating efficacy and these approaches arenot specific to stump or phantom pain. Mirror-box therapy hasdemonstrated mixed results and is not widely used in clinical practice.

Many surgical procedures have been attempted, but few are successful andmost are contraindicated for the majority of the amputee patients.Because neuromas may be implicated with stump and phantom pain, therehave been many attempts to remove them surgically, but ultimately a newneuroma usually develops each time a nerve is cut and the pain reliefonly lasts for the time that it takes for a new neuroma to form, usuallyabout three weeks. Furthermore, neuroablative procedures carry the riskof producing deafferentation pain, and any surgical procedure has agreater chance of failure than success. Thus, present medical treatmentsof stump and phantom pain are inadequate, and most sufferers resort toliving with pain that is poorly controlled with medications.

Electrical stimulation systems hold promise for relief ofpost-amputation pain, but widespread use of available systems islimited.

Transcutaneous electrical nerve stimulation (TENS) has been cleared bythe FDA for treatment of pain. TENS systems are externalneurostimulation devices that use electrodes placed on the skin surfaceto activate target nerves below the skin surface. TENS has a low rate ofserious complications, but it also has a relatively low (i.e., less than25%) long-term rate of success.

Application of TENS has been used to treat pain successfully, but it haslow long-term patient compliance, because it may cause additionaldiscomfort by generating cutaneous pain signals due to the electricalstimulation being applied through the skin, and the overall system isbulky, cumbersome, and not suited for long-term use.

In addition, several clinical and technical issues associated withsurface electrical stimulation have prevented it from becoming a widelyaccepted treatment method. First, stimulation of cutaneous painreceptors cannot be avoided resulting in stimulation-induced pain thatlimits patient tolerance and compliance. Second, electrical stimulationis delivered at a relatively high frequency to preventstimulation-induced pain, which leads to early onset of muscle fatiguein turn preventing patients from properly using their arm. Third, it isdifficult to stimulate deep nerves and/or muscles with surfaceelectrodes without stimulating overlying, more superficial nerves and/ormuscles resulting in unwanted stimulation. Finally, clinical skill andintensive patient training is required to place surface electrodesreliably on a daily basis and adjust stimulation parameters to provideoptimal treatment. The required daily maintenance and adjustment of asurface electrical stimulation system is a major burden on both patientand caregiver.

Spinal cord stimulation (SCS) systems are FDA approved as implantableneurostimulation devices marketed in the United States for treatment ofpain. Similar to TENS, when SCS evokes paresthesias that cover theregion of pain, it confirms that the location of the electrode and thestimulus intensity should be sufficient to provide pain relief and painrelief can be excellent initially, but maintaining sufficientparesthesia coverage is often a problem as the lead migrates along thespinal canal.

Spinal cord stimulation is limited by the invasive procedure and thedecrease in efficacy as the lead migrates. When it can produceparesthesias in the region of pain, spinal cord stimulation is typicallysuccessful initially in reducing pain, but over time the paresthesiacoverage and pain reduction is often lost as the lead migrates away fromits target.

Lead migration is the most common complication for spinal cordstimulators occurring in up to 45-88% of the cases. When the leadmigrates, the active contact moves farther from the target fibers andloses the ability to generate paresthesias in the target area. SCSsystems attempt to address this problem by using leads with multiplecontacts so that as the lead travels, the next contact in line can beselected to be the active contact. Peripheral nerve stimulation may beeffective in reducing pain, but it previously required specializedsurgeons to place cuff- or paddle-style leads around the nerves in atime consuming procedure.

Immediately following an amputation, all patients experience short-term(postoperative) pain, but it usually resolves within a month as thewound heals. In contrast, a long-term pain often develops and persistsin the residual limb, and may be perceived in the phantom limb, afterthe amputated limb has healed. Residual limb pain and phantom limb painare thought to have a peripheral and central component, and bothcomponents may be mediated by stimulating the peripheral nerves thatwere transected during amputation.

Neuromas develop when a peripheral nerve is cut and the proximal portionproduces new axon growth that forms a tangled mass as it fails toconnect with the missing distal portion of the nerve. All amputationsproduce neuromas and not all neuromas are painful, but neuromas arethought to be a major source of pain after amputation. Neuromas maygenerate spontaneous activity, and the level of activity in afferentfibers innervating the region of pain has been linked to the level ofpost-amputation pain.

As previously described, electrical stimulation has been used and shownto be effective in treating amputee pain, but present methods ofimplementation have practical limitations that prevent widespread use.External systems are too cumbersome, and implanted spinal cordstimulation systems often have problems of lead migration along thespinal canal, resulting in either the need for frequent reprogramming orclinical failure.

Percutaneous, intramuscular electrical stimulation for the treatment ofpost-stroke shoulder pain has been studied as an alternative to surfaceelectrical stimulation. A feasibility study and a pilot study showedsignificant reduction in pain and no significant adverse events whenusing percutaneous, intramuscular electrical stimulation in shouldermuscles.

This form of percutaneous, intramuscular electrical stimulation can becharacterized as “motor point” stimulation of muscle. To relieve pain inthe target muscle, the percutaneous lead is placed in the muscle that isexperiencing the pain near the point where a motor nerve enters themuscle (i.e., the motor point). In “motor point” stimulation of muscle,the muscle experiencing pain is the same muscle in which the lead isplaced. In “motor point” stimulation of muscle, the pain is felt andrelieved in the area where the lead is located.

SUMMARY OF THE INVENTION

The invention provides systems and methods for placing one or more leadsin tissue for providing electrical stimulation to tissue to treat painin a manner unlike prior systems and methods. Systems and methodsaccording to the present invention may be utilized to reduce pain, suchas that experienced by amputees. Most amputees have two types of pain:residual limb (stump) pain and phantom pain. The systems and methods ofthe present invention are adapted to reduce either and/or both types ofpain by stimulating target nerves of passage. It is to be appreciatedthat amputation may include any or all portions of a limb, including anyarm or leg in both humans and animals.

The invention provides systems and methods incorporate a discovery thatpain felt in a given region of the body can be treated, not by motorpoint stimulation of muscle in the local region where pain is felt, butby stimulating muscle close to a “nerve of passage” in a region that issuperior (i.e., cranial or upstream toward the spinal column) to theregion where pain is felt. Neural impulses comprising pain felt in agiven muscle or cutaneous region of the body pass through spinal nervesthat arise from one or more nerve plexuses. The spinal nerves in a nerveplexus, which comprise trunks that divide by divisions and/or cords intobranches, comprise “nerves of passage.” It has been discovered thatapplying stimulation in a muscle or other tissue (including adipose orconnective tissue) near a targeted nerve of passage relieves pain thatmanifests itself in a region that is inferior (i.e., caudal ordownstream from the spinal column) from where stimulation is actuallyapplied.

Phantom limb pain (one type of post-amputation pain) is one example ofthe effectiveness of “nerves of passage” stimulation, because the areafrom which phantom pain is perceived as emanating does not physicallyexist. A lead cannot be physically placed in the region (s) (e.g.muscles and/or other tissues and/or structures including adipose tissue,bones, joints, ligaments, connective tissue) that hurt, because thoseregions (e.g. muscles and/or other tissues) were amputated. Still, byapplying stimulation in a region (e.g. a muscle and/or other tissueincluding adipose) that has not been amputated near a targeted nerve ofpassage that, before amputation, natively innervated the amputatedregion(s), phantom limb pain can be treated.

Chronic or acute pain in existing, non-amputated muscles can also betreated by “nerves of passage” stimulation. By applying stimulation inan existing muscle near a targeted nerve of passage that caudallyinnervates the region where chronic or acute pain is manifested, thepain can be treated.

In “nerves of passage” stimulation, an electrode, which may be supportedon a wire lead, can be placed in a muscle or other tissue that isconveniently located near a nerve trunk that passes by the lead on theway to the painful area. On “nerves of passage” stimulation, the lead isplaced in a muscle that is not the target (painful) muscle, but rather amuscle that is upstream from the painful region, because the proximalmuscle presents a convenient and useful location to place the lead orelectrode.

The systems and methods make possible the treatment of pain (e.g. acute,sub-acute or sub-chronic, and/or chronic) in which cases musclecontraction cannot be evoked or is otherwise undesirable (e.g. in thecase of amputation pain in which the target area has been amputated isno longer physically present), or other cases of nerve damage either dueto a degenerative diseases or condition such as diabetes of impairedvascular function (in which the nerves are slowly degenerating,progressing from the periphery), or due to other disorders, trauma,surgery or other reasons it may be undesirable or is contra-indicated toplace an electrode or lead in or near that region(s) of pain. Thesystems and methods make possible the placement stimulation leads inregions distant from the motor point or region of pain, e.g., whereeasier access or more a reliable access or clinician-preferred access beaccomplished; or in situations where the motor nerve point is notavailable, damaged, traumatized, or otherwise not desirable; or insituations where it is desirable to stimulate more than one motor pointwith a single lead; or for cosmetic reasons; or to shorten the distancebetween the lead and its connection with a pulse generator; or to avoidtunneling over a large area. Additionally, where only a single electrodeis utilized, risks of complications and number of system components maybe minimized.

Other types of pain may also be treated according to the presentinvention, including without limitation neuropathic pain, post-surgicalpain (e.g. pain following knee surgery or total knee arthroplasty(TKA)), joint pain, complex regional pain syndrome (CRPS), andneuropathies (such as diabetic neuropathy)

Other features and advantages of the inventions are set forth in thefollowing specification and attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B are schematic anatomic views, respectively anterior andlateral, of a human peripheral nervous system.

FIG. 2A is a schematic anatomic view of a human spine, showing thevarious regions and the vertebrae comprising the regions.

FIGS. 2B and 2C are schematic anatomic views of the dermatome boundariesof a human.

FIGS. 3A, 3B, and 3C are anatomic views of the intercostal spinal nervesof a human.

FIGS. 4A and 4B are anatomic views of the spinal nerves of the brachialplexus.

FIG. 5 is an anatomic views of the spinal nerves of the lumbar plexus.

FIG. 6 is an anatomic view of the spinal nerves of the sacral plexus.

FIG. 7 is an anatomic view of the spinal nerves of the cervical plexus.

FIG. 8 is an anatomic view of the spinal nerves of the solar plexus.

FIG. 9 is an idealized, diagrammatic view showing a motor pointstimulation system.

FIG. 10 is an idealized, diagrammatic view showing a nerve of passagestimulation system.

FIGS. 11A to 11D are views showing a percutaneous lead that can form apart of a nerve of passage stimulation system.

FIG. 12 is a view of a package containing a nerve of passage stimulationsystem.

FIGS. 13A-B and 14A-B are representative leads that can form a part of anerve of passage stimulation system.

FIGS. 15A and 15B are schematic anatomic views of a system for applyingnerve of passage stimulation to spinal nerves in the brachial plexus.

FIGS. 16A, 16B, and 16C are schematic anatomic views of a system forapplying nerve of passage stimulation to a femoral nerve.

FIGS. 17A, 17B, and 17C are schematic anatomic views of a system forapplying nerve of passage stimulation to a sciatic/tibial nerve.

FIGS. 18A and 18B are schematic sectional anatomic views of systems forapplying nerve of passage stimulation to a femoral nerve and asciatic/tibial nerve.

FIGS. 19A, 19B, and 19C are schematic sectional anatomic views of asystem for applying nerve of passage stimulation along a sciatic/tibialnerve.

FIG. 20 is an elevation view of an embodiment of a percutaneous leadaccording to the present invention.

FIG. 21 is a perspective view of an introducer according to the presentinvention.

FIG. 22 is a perspective view of the introducer of FIG. 21 loaded withthe lead of FIG. 20 .

FIG. 23A is a perspective view of an EMG needle insertion towards ahuman femoral nerve.

FIG. 23B is a perspective view of an insertion of the embodiment of FIG.22 towards a human femoral nerve.

FIG. 24 is a superior cross-sectional view of a right human leg afterelectrode insertion.

FIG. 25 is a graph of daily-reported worst pain felt over previoustwenty-four hours as reported over an eight-week period, including atwo-week initial baseline period, a two-week stimulation period, and afour-week follow-up period

FIG. 26 is a table indicating outcome measures collected during baseline(Visit 1), after the first week of stimulation (Visit 3), after thesecond week of stimulation (Visit 4), after the first week of follow-up(F/U) (Visit 5), and after the fourth week of follow-up (Visit 6).Percent change from baseline is reported in parentheses (%) whereapplicable.

FIG. 27 is a graph showing a progression of self-reported residual limbpain intensities for six patients averaged over seven days up toforty-two days from start of a pain relief method according to thepresent invention.

FIG. 28 is a graph showing a percent of improvement, i.e., percentreduction, of residual limb pain for the six patients whose painintensities were diagrammed in FIG. 27 .

FIG. 29 is a graph showing a progression of self-reported phantom limbpain intensities for three patients (two of which were also diagrammedin FIG. 27 ) averaged over seven days up to forty-two days from start ofa pain relief method according to the present invention.

FIG. 30 is a graph showing a percent of improvement, i.e., percentreduction, of phantom limb pain for the three patients whose painintensities were diagrammed in FIG. 29 .

FIG. 31 is a diagrammatic representation of conventional peripheralnerve stimulation electrode placement on a nerve trunk.

FIG. 32 is a diagrammatic representation of an electrode placementaccording to the present invention.

FIG. 33 is a first graph depicting a widening therapeutic window forstimulation amplitude variability of methods according to the presentinvention.

FIG. 34 is a second graph depicting a widening therapeutic window forstimulation amplitude variability of methods according to the presentinvention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Although the disclosure hereof is detailed and exact to enable thoseskilled in the art to practice the invention, the physical embodimentsherein disclosed merely exemplify the invention which may be embodied inother specific structures. While the preferred embodiment has beendescribed, the details may be changed without departing from theinvention, which is defined by the claims.

Any elements described herein as singular can be pluralized (i.e.,anything described as “one” can be more than one). Any species elementof a genus element can have the characteristics or elements of any otherspecies element of that genus. The described configurations, elements orcomplete assemblies and methods and their elements for carrying out theinvention, and variations of aspects of the invention can be combinedand modified with each other in any combination.

I. The Peripheral Nervous System

(Anatomic Overview)

As generally shown in FIGS. 1A and 1B, the peripheral nervous systemconsists of nerve fibers and cell bodies outside the central nervoussystem (the brain and the spinal column) that conduct impulses to oraway from the central nervous system. The peripheral nervous system ismade up of nerves (called spinal nerves) that connect the centralnervous system with peripheral structures. The spinal nerves of theperipheral nervous system arise from the spinal column and exit throughintervertebral foramina in the vertebral column (spine). The afferent,or sensory, fibers of the peripheral nervous system convey neuralimpulses to the central nervous system from the sense organs (e.g., theeyes) and from sensory receptors in various parts of the body (e.g., theskin, muscles, etc.). The efferent, or motor, fibers convey neuralimpulses from the central nervous system to the effector organs (musclesand glands).

The somatic nervous system (SNS) is the part of the peripheral nervoussystem associated with the voluntary control of body movements throughthe action of skeletal muscles, and with reception of external stimuli,which helps keep the body in touch with its surroundings (e.g., touch,hearing, and sight). The system includes all the neurons connected withskeletal muscles, skin and sense organs. The somatic nervous systemconsists of efferent nerves responsible for sending central nervoussignals for muscle contraction. A somatic nerve is a nerve of thesomatic nervous system.

A. Spinal Nerves

A typical spinal nerve arises from the spinal cord by rootlets whichconverge to form two nerve roots, the dorsal (sensory) root and theventral (motor) root. The dorsal and ventral roots unite into a mixednerve trunk that divides into a smaller dorsal (posterior) primary ramusand a much larger ventral (anterior) primary ramus. The posteriorprimary rami serve a column of muscles on either side of the vertebralcolumn, and a narrow strip of overlying skin. All of the other muscleand skin is supplied by the anterior primary rami.

The nerve roots that supply or turn into peripheral nerves can begenerally categorized by the location on the spine where the roots exitthe spinal cord, i.e., as generally shown in FIG. 2A, cervical(generally in the head/neck, designated C1 to CB), thoracic (generallyin chest/upper back, designated T1 to T12), lumbar (generally in lowerback, designated L1 to LS); and sacral (generally in the pelvis,designated S1 to SS). All peripheral nerves can be traced back (towardthe spinal column) to one or more of the spinal nerve roots in eitherthe cervical, thoracic, lumbar, or sacral regions of the spine. Theneural impulses comprising pain felt in a given muscle or cutaneousregion of the body pass through spinal nerves and (usually) one or morenerve plexuses. For this reason, the spinal nerves will sometimes becalled in shorthand for the purpose of description “nerves of passage.”The spinal nerves begin as roots at the spine, and can form trunks thatdivide by divisions or cords into branches that innervate skin andmuscles.

Spinal nerves have motor fibers and sensory fibers. The motor fibersinnervate certain muscles, while the sensory fibers innervate anystructure or tissue that has sensation, which may include muscle. A skinarea innervated by the sensory fibers of a single nerve root is known asa dermatome. A group of muscles primarily innervated by the motor fibersof a single nerve root is known as a myotome. Although slight variationsdo exist, dermatome and myotome patterns of distribution are relativelyconsistent from person to person. It is to be understood that, althoughmuscles and skin are discussed as examples, nerves also innervate othernearby structures such as joints, bones, adipose tissue, connectivetissue, etc. For example, portions or branches of the sciatic andfemoral nerves do not innervate only the muscles and skin of the lowerextremity, they also innervate the bone, joints, adipose tissue,connective tissue, etc., and treatment of pain therein is alsocontemplated hereby.

Each muscle in the body is supplied by a particular level or segment ofthe spinal cord and by its corresponding spinal nerve. The muscle, andits nerve make up a myotome. This is approximately the same for everyperson and are as follows:

-   -   C3,4 and S supply the diaphragm (the large muscle between the        chest and the belly that we use to breath).    -   CS also supplies the shoulder muscles and the muscle that we use        to bend our elbow.    -   C6 is for bending the wrist back. C7 is for straightening the        elbow.    -   CB bends the fingers.    -   T1 spreads the fingers.    -   T1-T12 supplies the chest wall & abdominal muscles. L2 bends the        hip.    -   L3 straightens the knee.    -   L4 pulls the foot up. LS wiggles the toes.    -   S1 pulls the foot down.    -   S3,4 and S supply the bladder, bowel, and sex organs and the        anal and other pelvic muscles.

Dermatome is a Greek word which literally means “skin cutting”. Adermatome is an area of the skin supplied by nerve fibers originatingfrom the dorsal nerve root(s). The dermatomes are named according to thespinal nerve which supplies them. The dermatomes form into bands aroundthe trunk (see FIGS. 2B and 2C), but in the limbs their organization canbe more complex as a result of the dermatomes being “pulled out” as thelimb buds form and develop into the limbs during embryologicaldevelopment.

In the diagrams or maps shown in FIGS. 2B and 2C, the boundaries ofdermatomes are usually sharply defined. However, in life there isconsiderable overlap of innervation between adjacent dermatomes. Thus,if there is a loss of afferent nerve function by one spinal nervesensation from the region of skin which it supplies is not usuallycompletely lost as overlap from adjacent spinal nerves occurs; however,there may be a reduction in sensitivity.

B. Intercostal Nerves

The intercostal nerves (see FIGS. 3A, 3B, and J C) are the anteriordivisions of the thoracic spinal nerves from the thoracic vertebrae T1to T11. The intercostal nerves are distributed chiefly to the thoracicpleura and abdominal peritoneum and differ from the anterior divisionsof the other spinal nerves in that each pursues an independent coursewithout plexus formation.

The first two nerves supply fibers to the upper limb in addition totheir thoracic branches; the next four are limited in their distributionto the parietes of the thorax; the lower five supply the parietes of thethorax and abdomen. The 7th intercostal nerve terminates at the xyphoidprocess, at the lower end of the sternum. The 10th intercostal nerveterminates at the umbilicus. The twelfth (subcostal) thoracic isdistributed to the abdominal wall and groin.

Branches of a typical intercostal nerve include the ventral primaryramus; lateral cutaneous branches that pass beyond the angles of therubs and innervate the internal and external intercostal musclesapproximately halfway around the thorax; and the anterior cutaneousbranches that supply the skin on the anterior aspect of the thorax andabdomen.

C. Spinal Nerve Plexuses

A nerve plexus is a network of intersecting anterior primary rami. Thesets of anterior primary rami form nerve trunks that ultimately furtherdivide through divisions and then into cords and then into nervebranches serving the same area of the body. The nerve branches aremixed, i.e., they carry both motor and sensory fibers. The branchesinnervate the skin, muscle, or other structures. One example of theentry of a terminal motor nerve branch into muscle is called a motorpoint.

As shown in FIGS. 1A and 1B, there are several nerve plexuses in thebody, including (i) the brachial plexus, which serves the chest,shoulders, arms and hands; (ii) the lumbar plexus, which serves theback, abdomen, groin, thighs, knees, and calves; (iii) the sacralplexus, which serves the buttocks, thighs, calves, and feet; (iv) thecervical plexus, which serves the head, neck and shoulders; and (vi) thesolar plexus, which serves internal organs. The following describes,from an anatomic perspective, the spinal nerves of passage passingthrough the various plexuses, and the muscle and/or skin regions theyinnervate and where pain can be felt.

1. The Brachial Plexus

Most nerves in the upper limb arise from the brachial plexus, as shownin FIGS. 4A and 4B. The brachial plexus begins in the neck (vertebrae CSthrough C7), forms trunks, and extends through divisions and cords intothe axilla (underarm), where nearly all the nerve branches arise.Primary nerve branches of the brachial plexus include themusculocutaneous nerve; the median nerve; the ulnar nerve; the axillarynerve; and the radial nerve.

a. The Musculocutaneous Nerve

The musculocutaneous nerve arises from the lateral cord of the brachialplexus. Its fibers are derived from cervical vertebrae CS, C6. Themusculocutaneous nerve penetrates the coracobrachialis muscle and passesobliquely between the biceps brachii and the brachialis, to the lateralside of the arm. Just above the elbow, the musculocutaneous nervepierces the deep fascia lateral to the tendon of the biceps brachiicontinues into the forearm as the lateral antebrachial cutaneous nerve.In its course through the arm, the musculocutaneous nerve innervates thecoracobrachialis, biceps brachii, and the greater part of thebrachialis.

b. The Median Nerve

The median nerve is formed from parts of the medial and lateral cords ofthe brachial plexus, and continues down the arm to enter the forearmwith the brachial artery. It originates from the brachial plexus withroots from cervical vertebrae CS, C6, C7 and thoracic vertebra T1. Themedian nerve innervates all of the flexors in the forearm, except flexorcarpi ulnaris and that part of flexor digitorum profundus that suppliesthe medial two digits. The latter two muscles are supplied by the ulnarnerve of the brachial plexus. The median nerve is the only nerve thatpasses through the carpal tunnel, where it may be compressed to causecarpal tunnel syndrome.

The main portion of the median nerve supplies the following muscles: (i)the superficial group comprising pronator teres muscle; flexor carpiradialis muscle; palmaris longus muscle; and (ii) the intermediate groupcomprising flexor digitorum superficialis muscle.

The anterior interosseus branch of the median nerve supplies the deepgroup comprising flexor digitorum profundus muscle (lateral half);flexor pollicis longus muscle; and pronator quadratus.

In the hand, the median nerve supplies motor innervation to the 1st and2nd lumbrical muscles. It also supplies the muscles of the thenareminence by a recurrent thenar branch. The rest of the intrinsic musclesof the hand are supplied by the ulnar nerve of the brachial plexus.

The median nerve innervates the skin of the palmar side of the thumb,the index and middle finger, half the ring finger, and the nail bed ofthese fingers. The lateral part of the palm is supplied by the palmarcutaneous branch of the median nerve, which leaves the nerve proximal tothe wrist creases. The palmar cutaneous branch travels in a separatefascial groove adjacent to the flexor carpi radialis and thensuperficial to the flexor retinaculum. It is therefore spared in carpaltunnel syndrome.

c. The Ulnar Nerve

The ulnar nerve comes from the medial cord of the brachial plexus, anddescends on the posteromedial aspect of the humerus. It goes behind themedial epicondyle, through the cubital tunnel at the elbow (where it isvulnerable to injury for a few centimeters, just above the joint). Onemethod of injuring the nerve is to strike the medial epicondyle of thehumerus from posteriorly, or inferiorly with the elbow flexed. The ulnarnerve is trapped between the bone and the overlying skin at this point.This is commonly referred to as hitting one's “funny bone.”

The ulnar nerve is the largest nerve not protected by muscle or bone inthe human body. The ulnar nerve is the only unprotected nerve that doesnot serve a purely sensory function. The ulnar nerve is directlyconnected to the little finger, and the adjacent half of the ringfinger, supplying the palmar side of these fingers, including both frontand back of the tips, as far back as the fingernail beds.

The ulnar nerve and its branches innervate muscles in the forearm andhand. In the forearm, the muscular branches of ulnar nerve innervatesthe flexor carpi ulnaris and the flexor digitorum profundus (medialhalf). In the hand, the deep branch of ulnar nerve innervates hypothenarmuscles; opponens digiti minimi; abductor digiti minimi; flexor digitiminimi brevis; adductor pollicis; flexor pollicis brevis (deep head);the third and fourth lumbrical muscles; dorsal interossei; palmarinterossei. In the hand, the superficial branch of ulnar nerveinnervates palmaris brevis.

The ulnar nerve also provides sensory innervation to the fifth digit andthe medial half of the fourth digit, and the corresponding part of thepalm. The Palmar branch of ulnar nerve supplies cutaneous innervation tothe anterior skin and nails. The dorsal branch of ulnar nerve suppliescutaneous innervation to the posterior skin (except the nails).

d. The Axillary Nerve

The axillary nerve comes off the posterior cord of the brachial plexusat the level of the axilla (armpit) and carries nerve fibers fromvertebrae CS and C6. The axillary nerve travels through the quadrangularspace with the posterior circumflex humeral artery and vein. It suppliestwo muscles: the deltoid (a muscle of the shoulder), and the teres minor(one of the rotator cuff muscles). The axillary nerve also carriessensory information from the shoulder joint, as well as from the skincovering the inferior region of the deltoid muscle, i.e., the“regimental badge” area (which is innervated by the superior lateralcutaneous nerve branch of the axillary nerve). When the axillary nervesplits off from the posterior cord, the continuation of the cord is theradial nerve.

e. The Radial Nerve

The radial nerve supplies the upper limb, supplying the triceps brachiimuscle of the arm, as well as all twelve muscles in the posteriorosteofascial compartment of the forearm, as well as the associatedjoints and overlying skin. The radial nerve originates from theposterior cord of the brachial plexus with roots from cervical vertebraeCS, C6, C7, CB and thoracic vertebra T1.

Cutaneous innervation is provided by the following nerves: (i) posteriorcutaneous nerve of arm (originates in axilla); (ii) inferior lateralcutaneous nerve of arm (originates in arm); and (iii) posteriorcutaneous nerve of forearm (originates in arm). The superficial branchof the radial nerve provides sensory innervation to much of the back ofthe hand, including the web of skin between the thumb and index finger.

Muscular branches of the radial nerve innervate the triceps brachii;anconeus brachioradialis; and the extensor carpi radialis longus.

The deep branch of the radial nerve innervates the extensor carpiradialis brevis; supinator; posterior interosseous nerve (a continuationof the deep branch after the supinator): extensor digitorum; extensordigiti minimi; extensor carpi ulnaris; abductor pollicis longus;extensor pollicis brevis; extensor pollicis longus; and extensorindicis.

The radial nerve (and its deep branch) provides motor innervation to themuscles in the posterior compartment of the arm and forearm, which aremostly extensors.

2. Sacral and Lumbar Plexuses

The lumbar plexus (see FIG. 5 ) is a nervous plexus in the lumbar regionof the body and forms part of the lumbosacral plexus. It is formed bythe ventral divisions of the first four lumbar nerves (L1-L4) and fromcontributions of the subcostal thoracic nerve (T12), which is the last(most inferior) thoracic nerve.

Additionally, the ventral rami of sacral vertebrae S2 and SJ nervesemerge between digitations of the piriformis and coccygeus nuscles. Thedescending part of the lumbar vertebrae L4 nerve unites with the ventralramus of the lumbar vertebrae LS nerve to form a thick, cordlikelumbosacral trunk. The lumbosacral trunk joins the sacral plexus (seeFIG. 6 ). The main nerves of the lower limbs arise from the lumbar andsacral plexuses.

a. Nerves of the Sacral Plexus

The sacral plexus provides motor and sensory nerves for the posteriorthigh, most of the lower leg, and the entire foot.

(1) The Sciatic Nerve

As shown in FIGS. 1A and 6 , the sciatic nerve (also known as theischiatic nerve) arises from the sacral plexus. It is the longest andwidest single nerve in the human body. It begins in the lower back andruns through the buttock and down the lower limb. The sciatic nervesupplies nearly the whole of the skin of the leg, the muscles of theback of the thigh, and those of the leg and foot. It is derived fromspinal nerves L4 through SJ. It contains fibers from both the anteriorand posterior divisions of the lumbosacral plexus.

The nerve gives off articular and muscular branches. The articularbranches (rami articulares) arise from the upper part of the nerve andsupply the hip-joint, perforating the posterior part of its capsule;they are sometimes derived from the sacral plexus. The muscular branches(rami musculares) innervate the following muscles of the lower limb:biceps femoris, semitendinosus, semimembranosus, and adductor magnus.The nerve to the short head of the biceps femoris comes from the commonperoneal part of the sciatic, while the other muscular branches arisefrom the tibial portion, as may be seen in those cases where there is ahigh division of the sciatic nerve.

The muscular branch of the sciatic nerve eventually gives off the tibialnerve (shown in FIG. 1A) and common peroneal nerve (also shown in FIG.1A), which innervates the muscles of the (lower) leg. The tibial nervegoes on to innervate all muscles of the foot except the extensordigitorum brevis (which is innervated by the peroneal nerve).

Two major branches of the sciatic nerve are the tibial and commonperoneal nerves that innervate much of the lower leg (around and belowthe knee). For example, the tibial nerve innervates the gastrocnemius,popliteus, soleus and plantaris muscles and the knee joint. Most of thefoot is innervated by the tibial and peroneal nerve.

b. Nerves of the Lumbar Plexus

The lumbar plexus (see FIG. 5 ) provides motor, sensory, and autonomicfibres to gluteal and inguinal regions and to the lower extremities. Thegluteal muscles are the three muscles that make up the buttocks: thegluteus maximus muscle, gluteus medius muscle and gluteus minimusmuscle. The inguinal region is situated in the groin or in either of thelowest lateral regions of the abdomen.

(1) The Iliohypogastric Nerve

The iliohypogastric nerve (see FIG. 5 ) runs anterior to the psoas majoron its proximal lateral border to run laterally and obliquely on theanterior side of quadratus lumborum. Lateral to this muscle, it piercesthe transversus abdominis to run above the iliac crest between thatmuscle and abdominal internal oblique. It gives off several motorbranches to these muscles and a sensory branch to the skin of thelateral hip. Its terminal branch then runs parallel to the inguinalligament to exit the aponeurosis of the abdominal external oblique abovethe external inguinal ring where it supplies the skin above the inguinalligament (i.e. the hypogastric region) with the anterior cutaneousbranch.

(2) The Ilioinguinal Nerve

The ilioinguinal nerve (see FIG. 5 ) closely follows the iliohypogastricnerve on the quadratus lumborum, but then passes below it to run at thelevel of the iliac crest. It pierces the lateral abdominal wall and runsmedially at the level of the inguinal ligament where it supplies motorbranches to both transversus abdominis and sensory branches through theexternal inguinal ring to the skin over the pubic symphysis and thelateral aspect of the labia majora or scrotum.

(3) The Genitofemoral Nerve

The genitofemoral nerve (see FIG. 5 ) pierces psoas major anteriorlybelow the former two nerves to immediately split into two branches thatrun downward on the anterior side of the muscle. The lateral femoralbranch is purely sensory. It pierces the vascular lacuna near thesaphenous hiatus and supplies the skin below the inguinal ligament (i.e.proximal, lateral aspect of femoral triangle). The genital branchdiffers in males and females. In males it runs in the spermatic cord andin females in the inguinal canal together with the teres uteri ligament.It then sends sensory branches to the scrotal skin in males and thelabia majora in females. In males it supplies motor innervation to thecremaster.

(4) The Lateral Cutaneous Femoral Nerve

The lateral cutaneous femoral nerve (see FIG. 5 ) pierces psoas major onits lateral side and runs obliquely downward below the iliac fascia.Medial to the anterior superior iliac spine it leaves the pelvic areathrough the lateral muscular lacuna. In the thigh it briefly passesunder the fascia lata before it breaches the fascia and supplies theskin of the anterior thigh.

(5) The Obturator Nerve

The obturator nerve (see FIG. 5 ) leaves the lumbar plexus and descendsbehind psoas major on it medial side, then follows the linea terminalisand exits through the obturator canal. In the thigh, it sends motorbranches to obturator externus before dividing into an anterior and aposterior branch, both of which continues distally. These branches areseparated by adductor brevis and supply all thigh adductors with motorinnervation: pectineus, adductor longus, adductor brevis, adductormagnus, adductor minimus, and gracilis. The anterior branch contributesa terminal, sensory branch which passes along the anterior border ofgracilis and supplies the skin on the medial, distal part of the thigh.

(6) The Femoral Nerve

The femoral nerve (see FIG. 5 and also FIG. 16A) is the largest andlongest nerve of the lumbar plexus. It gives motor innervation toiliopsoas, pectineus, sartorius, and quadriceps femoris; and sensoryinnervation to the anterior thigh, posterior lower leg, and hindfoot. Itruns in a groove between psoas major and iliacus giving off branches toboth muscles. In the thigh it divides into numerous sensory and muscularbranches and the saphenous nerve, its long sensory terminal branch whichcontinues down to the foot.

The femoral nerve has anterior branches (intermediate cutaneous nerveand medial cutaneous nerve) and posterior branches. The saphenous nerve(branch of the femoral nerve) provides cutaneous (skin) sensation in themedial leg. Other branches of the femoral nerve innervate structures(such as muscles, joints, and other tissues) in the thigh and around thehip and knee joints. As an example, branches of the femoral nerveinnervate the hip joint, knee joint, and the four parts of theQuadriceps femoris (muscle) Rectus femoris (in the middle of the thigh)originates on the ilium and covers most of the other three quadricepsmuscles. Under (or deep to) the rectus femoris are the other 3 of thequadriceps muscles, which originate from the body of the femur. Vastuslateralis (on the outer side of the thigh) is on the lateral side of thefemur. Vastus medialis (on the inner part thigh) is on the medial sideof the femur. Vastus intermedius (on the top or front of the thigh) liesbetween vastus lateralis and vastus medialis on the front of the femur.Branches of the femoral nerve often innervate the pectineus andSartorius muscles arises.

3. The Cervical Plexus

The cervical plexus (see FIG. 7 ) is a plexus of the ventral rami of thefirst four cervical spinal nerves which are located from C1 to C4cervical segment in the neck. They are located laterally to thetransverse processes between prevertebral muscles from the medial sideand vertebral (m. scalenus, m. levator scapulae, m. splenius cervicis)from lateral side. Here there is anastomosis with accessory nerve,hypoglossal nerve and sympathetic trunk.

The cervical plexus is located in the neck, deep to sternocleidomastoid.Nerves formed from the cervical plexus innervate the back of the head,as well as some neck muscles. The branches of the cervical plexus emergefrom the posterior triangle at the nerve point, a point which liesmidway on the posterior border of the Sternocleidomastoid.

The nerves formed by the cervical plexus supply the back of the head,the neck and the shoulders. The face is supplied by a cranial nerve, thetrigeminal nerve. The upper four posterior primary rami are larger thanthe anterior primary rami. The C1 posterior primary ramus does notusually supply the skin. The C2 posterior primary ramus forms thegreater occipital nerve which supplies the posterior scalp. The upperfour anterior primary rami form the cervical plexus. The cervical plexussupplies the skin over the anterior and lateral neck to just below theclavicle. The plexus also supplies the muscles of the neck including thescalenes, the strap muscles, and the diaphragm.

The cervical plexus has two types of branches: cutaneous and muscular.

The cutaneous branches include the lesser occipital nerve, whichinnervates lateral part of occipital region (C2 nerve only); the greatauricular nerve, which innervates skin near concha auricle and externalacoustic meatus (C2 and CJ nerves); the transverse cervical nerve, whichinnervates anterior region of neck (C2 and CJ nerves); and thesupraclavicular nerves, which innervate region of suprascapularis,shoulder, and upper thoracic region (CJ, C4 Nerves)

The muscular branches include the ansa cervicalis (loop formed fromC1-CJ), etc. (geniohyoid (C1 only), thyrohyoid (C1 only), sternothyroid,sternohyoid, omohyoid); phrenic (CJ-CS (primarily C4)), which innervatesthe diaphragm; the segmental branches (C1-C4), which innervate theanterior and middle scalenes.

4. The Solar Plexus

The solar plexus (see FIG. 8 ) is a dense cluster of nerve cells andsupporting tissue, located behind the stomach in the region of theceliac artery just below the diaphragm. It is also known as the celiacplexus. Rich in ganglia and interconnected neurons, the solar plexus isthe largest autonomic nerve center in the abdominal cavity. Throughbranches it controls many vital functions such as adrenal secretion andintestinal contraction.

Derived from the solar plexus are the phrenic plexus (producingcontractions of the diaphragm, and providing sensory innervation formany components of the mediastinum and pleura); the renal plexuses(affecting renal function); the spermatic plexus (affecting function ofthe testis); as well as the gastric plexus; the hepatic plexus; thesplenic plexus; the superior mesenteric plexus; and the aortic plexus.

II. The System

The various aspects of the invention will be described in connectionwith the placement of one or more leads 12 having one or more electrodes14, or leadless electrodes, in muscle or other tissue, and in electricalproximity but away from nerves, for improved recruitment of targetednerves for therapeutic purposes, such as for the treatment of pain. Thatis because the features and advantages that arise due to the inventionare well suited to this purpose. It is to be appreciated that regions ofpain can include any or all portions of the body, whether or not suchportion is physically present on the body at the time of stimulationaccording to the present invention, including arms, legs, and trunk inboth humans and animals. A portion may not be physically present on thebody due to amputation, resection, otherwise removed (e.g. trauma), orit may be congenitally missing.

A. Stimulation of Nerves of Passage

FIG. 9 shows a typical “motor point” system and method for stimulating anerve or muscle A by placing a lead 12(A) with its electrode 14(A) closeto motor point A. As previously described, a motor point A is thelocation where the innervating spinal nerve enters the muscle. At thatlocation, the electrical stimulation intensity required to elicit a fullcontraction is at the minimum. Any other electrode placement location inthe muscle located further from the motor point would require morestimulation intensity to elicit the same muscle contraction.

FIG. 10 shows a “nerves of passage” system and method, that is unlikethe “motor point” system and method shown in FIG. 9 , and whichincorporates the features of the invention. As shown in FIG. 10 , thesystem and method identifies a region where there is a localmanifestation of pain. The region of pain can comprise, e.g., skin,bone, a joint, connective tissue, muscle, or other tissue or structure.The system and method identify one or more spinal nerves that arelocated anatomically upstream or cranial to the region where pain ismanifested, through which neural impulses comprising the actionpotentials that will be interpreted as pain. A given spinal nerve thatis identified can comprise a nerve trunk located in a nerve plexus, or adivisions and/or a cord of a nerve trunk, or a nerve branch, providedthat it is upstream or cranial of where the nerve innervates the regionaffected by the pain. The given spinal nerve can be identified bymedical professionals using textbooks of human anatomy along with theirknowledge of the site and the nature of the pain or injury, as well asby physical manipulated and/or imaging, e.g., by ultrasound,fluoroscopy, or X-ray examination, of the region where pain ismanifested. A desired criteria of the selection includes identifying thelocation of tissue (e.g. muscle, adipose, connective, or other tissue)in electrical proximity to but spaced away from the nerve or passage,which can be accessed by placement of one or more stimulationelectrodes, aided if necessary by ultrasonic or electro-locationtechniques. The nerve identified comprises a targeted “nerve ofpassage.” The muscle identified comprises the “targeted tissue” or“targeted muscle.” In a preferred embodiment, the electrodes arepercutaneously inserted using percutaneous leads.

The system and method place the one or more leads 12(B) with itselectrode 14(B), or leadless electrodes, in the targeted tissue inelectrical proximity to but spaced away from the targeted nerve ofpassage. The system and method apply electrical stimulation through theone or more stimulation electrodes to electrically activate or recruitthe targeted nerve of passage that conveys the neural impulsescomprising the pain to the spinal column.

The system and method can apply electrical stimulation to nerves ofpassage throughout the body. For example, the nerves of passage cancomprise one or more spinal nerves in the brachia plexus, to treat painin the chest, shoulders, arms and hands; and/or one or more spinalnerves in the lumbar plexus, to treat pain in the back, abdomen, thighs,knees, and calves; and/or one or more spinal nerves in the sacralplexus, to treat pain in the buttocks, thighs, calves, and feet; and/orone or more spinal nerves in the cervical plexus, to treat pain in thehead, neck and shoulders; and/or one or more spinal nerves in the solarplexus, to treat pain or dysfunction in internal organs.

For example, if the pinky finger hurts, the system and method canidentify and stimulate the ulnar nerve at a location that it is upstreamor cranial of where the nerve innervates the muscle or skin of the pinkyfinger, e.g., in the palm of the hand, forearm, and/or upper arm. Ifelectrical stimulation activates the target nerve of passagesufficiently at the correct intensity, then the patient will feel acomfortable tingling sensation called a paresthesia in the same regionas their pain, which overlap with the region of pain and/or otherwisereduce pain.

It is to be appreciated that the sensation could be described with otherwords such as buzzing, thumping, etc. Evoking paresthesias in the regionof pain confirms correct lead placement and indicates stimulus intensityis sufficient to reduce pain. Inserting a lead 12 percutaneously allowsthe lead 12 to be placed quickly and easily, and placing the lead 12 ina peripheral location, i.e., muscle, where it is less likely to bedislodged, addresses the lead migration problems of spinal cordstimulation that result in decreased paresthesia coverage, decreasedpain relief, and the need for frequent patient visits for reprogramming.

Placing the lead 12 percutaneously in muscle in electrical proximity tobut spaced away from the targeted nerve of passage minimizecomplications related to lead placement and movement. In a percutaneoussystem, an electrode lead 12, such as a coiled fine wire electrode leadmay be used because it is minimally-invasive and well suited forplacement in proximity to a nerve of passage. The lead can be sized andconfigured to withstand mechanical forces and resist migration duringlong-term use, particularly in flexible regions of the body, such as theshoulder, elbow, and knee.

B. The Lead

As FIG. 11A shows, the electrode lead can comprise, e.g., a fine wireelectrode 14, paddle electrode, intramuscular electrode, orgeneral-purpose electrode, inserted via a needle introducer 30 orsurgically implanted in proximity of a targeted nerve of passage. Onceproper placement is confirmed, the needle introducer 30 may be withdrawn(as FIGS. 11B and 11C show), leaving the electrode in place. Stimulationmay also be applied through a penetrating electrode, such as anelectrode array comprised of any number (i.e., one or more) ofneedle-like electrodes that are inserted into the target site. In bothcases, the lead may placed using a needle-like introducer 30, allowingthe lead/electrode placement to be minimally invasive, though surgicalplacement could also be utilized.

In a representative embodiment, the lead 12 comprises a thin, flexiblecomponent made of a metal and/or polymer material. By “thin,” it ispreferred that the lead may be approximately 0.75 mm (0.030 inch) orless in diameter.

The lead 12 may comprise one or more conductors, e.g., one or morecoiled metal wires, disposed within an open or flexible elastomer core.The wire can be insulated, e.g., with a biocompatible polymer film, suchas polyfluorocarbon, polyimide, or parylene. The lead is desirablycoated with a textured, bacteriostatic material, which helps tostabilize the lead in a way that still permits easy removal at a laterdate and increases tolerance.

The lead 12 may be electrically insulated everywhere except at one(monopolar), or two (bipolar), or three (tripolar) or more, for example,conduction locations near its distal tip. Each of the conductionlocations may be connected to one or more conductors that run the lengthof the lead and lead extension 16 (see FIG. 11C), proving electricalcontinuity from the conduction location through the lead 12 to anexternal pulse generator or stimulator 28 (see FIG. 11C) or an implantedpulse generator or stimulator 28 (see FIG. 11D)

The conduction location or electrode 14 may comprise a de-insulated areaof an otherwise insulated conductor that runs the length of an entirelyinsulated electrode. The de-insulated conduction region of the conductorcan be formed differently, e.g., it can be wound with a different pitch,or wound with a larger or smaller diameter, or molded to a differentdimension. The conduction location or the electrode 14 may comprise aseparate material (e.g., metal or a conductive polymer) exposed to thebody tissue to which the conductor of the wire is electrically coupled.

The lead 12 is desirably provided in a sterile package 62 (see FIG. 12), and may be pre-loaded in the introducer needle 30. The package 62 cantake various forms and the arrangement and contents of the package 62.As shown in FIG. 12 , the package 62 comprises a sterile, wrappedassembly. The package 62 includes an interior tray made, e.g., from diecut cardboard, plastic sheet, or thermo-formed plastic material, whichhold the contents. The package 62 also desirably includes instructionsfor use 58 for using the contents of the package to carry out the leadlocation and placement procedures, as will be described in greaterdetail below.

The lead 12 desirably possess mechanical properties in terms offlexibility and fatigue life that provide an operating life free ofmechanical and/or electrical failure, taking into account the dynamicsof the surrounding tissue (i.e., stretching, bending, pushing, pulling,crushing, etc.). The material of the electrode 14 desirably discouragesthe in-growth of connective tissue along its length, so as not toinhibit its withdrawal at the end of its use. However, it may bedesirable to encourage the in-growth of connective tissue at the distaltip of the electrode, to enhance its anchoring in tissue.

One embodiment of the lead 12 shown in FIG. 13A may comprise a minimallyinvasive coiled fine wire lead 12 and electrode 14. The electrode 14 mayalso include, at its distal tip, an anchoring element 48. In theillustrated embodiment, the anchoring element 48 takes the form of asimple barb or bend (see also FIG. 11C). The anchoring element 48 issized and configured so that, when in contact with tissue, it takespurchase in tissue, to resist dislodgement or migration of the electrodeout of the correct location in the surrounding tissue. Desirably, theanchoring element 48 is prevented from fully engaging body tissue untilafter the electrode 14 has been correctly located and deployed.

An alternative embodiment of an electrode lead 12 shown in FIGS. 14A and14B, may also include, at or near its distal tip or region, one or moreanchoring element (s) 70. In the illustrated embodiment, the anchoringelement 70 takes the form of an array of shovel-like paddles or scallops76 proximal to the proximal-most electrode 14 (although a paddle 76 orpaddles could also be proximal to the distal most electrode 14, or couldalso be distal to the distal most electrode 14) The paddles 76 as shownare sized and configured so they will not cut or score the surroundingtissue. The anchoring element 70 is sized and configured so that, whenin contact with tissue, it takes purchase in tissue, to resistdislodgement or migration of the electrode out of the correct locationin the surrounding tissue (e.g., muscle 54). Desirably, the anchoringelement 70 is prevented from fully engaging body tissue until after theelectrode 14 has been deployed. The electrode is not deployed untilafter it has been correctly located during the implantation (leadplacement) process, as previously described. In addition, the lead 12may include one or more ink markings 74, 75 (shown in FIG. 14A) to aidthe physician in its proper placement.

Alternatively, or in combination, stimulation may be applied through anytype of nerve cuff (spiral, helical, cylindrical, book, flat interfacenerve electrode (FINE), slowly closing FINE, etc.), paddle (orpaddle-style) electrode lead, cylindrical electrode lead, and/or otherlead that is surgically or percutaneously placed within tissue at thetarget site.

In all cases, the lead may exit through the skin and connect with one ormore external stimulators 28 (shown in FIG. 11C), or the lead(s) may berouted subcutaneously to one or more implanted pulse generators 28(shown in FIG. 11D), or they may be connected as needed to internal andexternal coils for RF (Radio Frequency) wireless telemetrycommunications or an inductively coupled telemetry to control theimplanted pulse generator. As shown in FIG. 11D, the implanted pulsegenerator 28 may be located some distance (remote) from the electrode14, or an implanted pulse generator may be integrated with anelectrode(s) (not shown), eliminating the need to route the leadsubcutaneously to the implanted pulse generator.

The introducer 30 (see FIG. 11A) may be insulated along the length ofthe shaft, except for those areas that correspond with the exposedconduction surfaces of the electrode 14 housed inside the introducer 30.These surfaces on the outside of the introducer 30 are electricallyisolated from each other and from the shaft of the introducer 30. Thesesurfaces may be electrically connected to a connector 64 at the end ofthe introducer body (see FIG. 11A). This allows connection to anexternal stimulator 28 (shown in FIG. 11A) during the implantationprocess. Applying stimulating current through the outside surfaces ofthe introducer 30 provides a close approximation to the response thatthe electrode 14 will provide when it is deployed at the currentlocation of the introducer 30.

The introducer 30 may be sized and configured to be bent by hand priorto its insertion through the skin. This will allow the physician toplace lead 12 in a location that is not in an unobstructed straight linewith the insertion site. The construction and materials of theintroducer 30 allow bending without interfering with the deployment ofthe lead 12 and withdrawal of the introducer 30, leaving the lead 12 inthe tissue.

C. Insertion of the Lead

Representative lead insertion techniques will now be described to placean electrode lead 12 in a desired location in muscle in electricalproximity to but spaced away from a nerve of passage. It is this leadplacement that makes possible the stimulation of the targeted nerve ornerves of passage with a single lead 12 to provide pain relief.

Instructions for use 58 (see FIG. 12 ) can direct use of system andmethod for the placement of a lead 12 in muscle in electrical proximityto but spaced away from the nerve or nerves of passage for improvedrecruitment of target nerves, e.g., with the placement of one or moreleads 12. The instructions for use may include instructions for placinga lead 12 for the activation of the targeted nerve of passage in asystem for the relief of pain, for example. The instructions for use mayalso include instructions for recording stimulus parameters, includingintensity associated with a first sensation of stimulation, a firstnoticeable muscle contraction, and/or a maximum tolerable contraction atmultiple locations, which can be used to aid in determining desiredstimulation parameters for optimal stimulation. The instructions 58 can,of course vary. The instructions 58 may be physically present in a kitsholding the lead 12 (as FIG. 12 shows), but can also be suppliedseparately. The instructions 58 can be embodied in separate instructionmanuals, or in video or audio tapes, CD's, and DVD's. The instructions58 for use can also be available through an internet web page.

To determine the optimal placement for the lead 12, test stimulation maybe delivered through needle electrodes, and muscle responses may beobserved. The motor point (s) of the target muscle (s) may be locatedfirst in order to confirm that the muscles are innervated. Needleelectrodes may be used because they can be easily repositioned until theoptimal location to deliver stimulation is determined.

At least one electrode may be placed in muscle tissue at atherapeutically effective distance spaced from a targeted nerve ofpassage. By a “therapeutically effective distance” is meant that theelectrode is not placed against the targeted nerve of passage, butrather spaced therefrom, electrically coupled to the nerve through otherbodily tissue. The spacing is advantageous because it simplifiesplacement and stimulation procedures, reduces the risk of neurologicalinjury to the patient, shortens the procedure time, makes the method ofpain relief more robust and durable and less likely to fail or loseeffectiveness over time. Such placement also allows the electrode to beplaced in tissue more resistant to electrode migration or unwantedmovement and more tolerant of motion and short and/or long-term changesin electrode position relative to the targeted nerve. The lead may beinserted via the introducer in conventional fashion, which may besimilar in size and shape to a hypodermic needle. The introducer 30 maybe any size. In a preferred embodiment, the introducer 30 may range insize from 17 gauge to 26 gauge. Prior to inserting the introducer 30,the insertion site may be cleaned with a disinfectant (e.g. Betadine, 2%Chlorhexidine/80% alcohol, 10% povidone-iodine, or similar agent). Alocal anesthetic (s) may be administered topically and/or subcutaneouslyto the area in which the electrode and/or introducer will be inserted.

The position of the electrodes may be checked by imaging techniques,such as ultrasound, fluoroscopy, or X-rays. Following placement of thelead(s), the portion of the leads which exit the skin may be secured tothe skin using covering bandages and/or adhesives.

Electrical stimulation may be applied to the targeted nerve of passageduring and after placement of the electrode to determine whetherstimulation of the targeted nerve of passage can generate comfortablesensations or paresthesias that overlap with the region of pain and/orreduce pain. The pain may be perceived to be contained within a specificpart(s) of the body and/or it may be perceived to be located outside ofthe body, as may be the case in persons with amputations who havephantom limb pain or pain in the amputated (or phantom) limb (s).

In a percutaneous system 10 (as FIGS. 11A to 11D show, the lead 12 maybe percutaneously placed near the targeted nerve of passage and exit ata skin puncture site 16. A trial or screening test may be conducted in aclinical setting (e.g. an office of a clinician, a laboratory, aprocedure room, an operating room, etc.). During the trial, the lead iscoupled to an external pulse generator 28 and temporary percutaneousand/or surface return electrodes, to confirm paresthesia coverage and/orpain relief of the painful areas.

If the clinical screening test is successful, the patient may proceed toa home-trial coupled to an external pulse generator 28 (as shown in FIG.11C) and temporary percutaneous and/or surface return electrodes, todetermine if pain relief can be sustained in the home environment.

The trial period may range from minutes to hours to days to weeks tomonths. The preferred trial period may be between 3 and 21 days.

If either the screening test or home trial is unsuccessful, the lead 12may be quickly and easily removed.

However, if the screening test and/or home-trial are successful, thepatient's percutaneous system may be converted into a fully implantedsystem (as shown in FIG. 11D) by replacing the external pulse generatorwith an implantable pulse generator 28 (the housing of which serves as areturn electrode)

Alternatively, it may be preferred to use a percutaneous system(s) as atherapy without proceeding to a fully implantable system. It is also tobe appreciated that a home-trial is not a requirement for either thepercutaneous system or a fully implanted system.

The duration of therapy for a percutaneous system may range from minutesto days to weeks to months to multiple years, but a preferred embodimentincludes a duration ranging from 1 to 12 weeks.

Electrical stimulation is applied between the lead and return electrodes(uni-polar mode). Regulated current is the preferred type ofstimulation, but other type(s) of stimulation (e.g. non-regulatedcurrent such as voltage-regulated) may also be used. Multiple types ofelectrodes may be used, such as surface, percutaneous, and/orimplantable electrodes. The surface electrodes may be a standard shapeor they may be tailored if needed to fit the contour of the skin.

In a preferred embodiment of a percutaneous system, the surfaceelectrode(s) may serve as the anode(s) (or return electrode(s)), but thesurface electrode(s) may be used as the cathode (s) (active electrode(s)) if necessary. When serving as a return electrod(e), the location ofthe electrode(s) is not critical and may be positioned anywhere in thegeneral vicinity, provided that the current path does not cross theheart. If a surface electrode(s) serves as an active electrode(s), it(they) may be positioned near the target stimulation area(s) (e.g. onthe skin surface over the target nerve or passage).

The electrode lead may be placed via multiple types of approaches. Inone embodiment, the approach may be similar to needle placement forelectromyography (EMG). For example (as shown in FIG. 15A), if thetargeted nerve of passage includes nerves of the brachial plexus, theapproach can include:

-   -   1) Place the patient in a comfortable and/or appropriate        position with head turned away from the lead insertion site.    -   2) Prepare the lead insertion site with antiseptic and local        subcutaneous anesthetic (e.g., 2% lidocaine).    -   3) Locate the site of skin puncture with appropriate landmarks,        such as the clavical, coracoid process, and axilla, as        necessary.    -   4) Insert a sterile percutaneous electrode lead 12 preloaded in        the introducer needle 30 at a predetermined angle based on        landmarks used.    -   5) Place a surface stimulation return electrode in proximity of        the area in which the percutaneous lead 12 has been placed. Test        stimulation will be applied to the lead 12, with the surface        electrode providing a return path. The surface electrode may be        placed adjacent to the lead. Its position is not critical to the        therapy and it can be moved throughout the therapy to reduce the        risk of skin irritation.    -   6) Couple the lead 12 to the external pulse generator 28 and to        the return electrode. Set the desired stimulation parameters.        Test stimulation may be delivered using a current-regulated        pulse generator, for example. The external pulse generator 28        may be programmed to about 0.1 to about 10 milliamps (mA), a        pulse duration or width of about five to about fifty        microseconds (μs), a pulse frequency of about four to about 300        Hertz (Hz), and a preferred on-off duty cycle of about 25 to        about 90 percent (on vs. off), as a non-limiting example.        Alternatively, rather than have an on-off duty cycle, the        stimulation can be delivered constantly for a predetermined        treatment time, such as about two to six weeks.    -   7) Advance the introducer slowly until the patient reports the        first evoked sensation in the region experiencing pain.        Progressively reduce the stimulus amplitude and advance the        introducer more slowly until the sensation can be evoked in the        painful region at a predetermined stimulus amplitude (e.g.,        about 0.1-5.0 mA). Stop the advancement of the introducer, and        increase the stimulus amplitude in small increments (e.g., about        0.1-0.5 mA) until the stimulation-evoked tingling sensation        (paresthesia) expands to overlay the entire region of pain.    -   8) Withdraw the introducer 30, leaving the percutaneous lead 12        in proximity but away from the target nerve (see FIG. 15B).    -   9) Cover the percutaneous exit site and lead 12 with a bandage.        A bandage may also be used to secure the external portion of the        lead 12 (or an extension cable used to couple the lead 12 to the        external pulse generator) to the skin. It is expected the length        of time to place the lead 12 to be less than 10 minutes,        although the process may be shorter or longer.    -   10) Vary the stimulus amplitude in small steps (e.g., 0.1-0.5        mA) to determine the thresholds at which stimulation evokes        first sensation (TsEN), sensation (paresthesia) superimposed on        the region of pain (Tsup), muscle twitch (TMusl of the target        muscle (innervated or not innervated by the target nerve),        and/or maximum comfortable sensation (Tx). Query the patient at        each stimulus amplitude to determine sensation level, and        visually monitor muscle response. Record the results.    -   11) It is possible that stimulation intensity may need to be        increased slightly during the process due to causes such as        habituation or the patient becoming accustomed to sensation, but        the need for increased intensity is unlikely and usually only        occurs after several days to weeks to months as the tissue        encapsulates and the patient accommodates to stimulation. It is        to be appreciated that the need for increased intensity could        happen at any time, even years out, which would likely be due to        either lead migration or habituation, but may also be due        reasons ranging from nerve damage to plasticity/reorganization        in the central nervous system.    -   12) If paresthesias cannot be evoked with the initial lead        placement, redirect the introducer 30.    -   13) If sensations still cannot be evoked in a given patient,        then the muscle twitch response of the muscle innervated or not        innervated by the target nerve may be used to guide lead        placement and then increase stimulus intensity until sufficient        paresthesias are elicited in the painful region. Minimal muscle        contraction may be acceptable if it is well tolerated by the        patient in exchange for significant pain relief and if it does        not lead to additional discomfort or fatigue.    -   14) If stimulation evokes muscle contraction at a lower stimulus        threshold than paresthesia (e.g. if TMus Tsup) and contraction        leads to discomfort, then a lower stimulus frequency (e.g., 12        Hz) may be used because low frequencies (e.g., 4-20 Hz) have        been shown to minimize discomfort due to muscle contraction and        provide >50% relief of shoulder pain in stroke patients while        still inhibiting transmission of pain signals in the central        nervous system in animals. If continued muscle contraction leads        to pain due to fatigue, change the duty cycle, using parameters        shown to reduce muscle fatigue and related discomfort in the        upper extremity (e.g. 5 s ramp up, 10 s on, 5 s ramp down, 10 s        off).    -   15) If stimulation fails to elicit paresthesia in all areas of        pain, then a second percutaneous lead (not shown) may need to be        placed to stimulate the nerves that are not activated by the        first lead 12.    -   16)

If stimulation is successful, i.e., if the screening test and/orhome-trial are successful, the patient's percutaneous system (see FIG. 1) may be converted into a fully implanted system by replacing theexternal pulse generator 28 with an implantable pulse generator that isimplanted in a convenient area (see FIG. 11D) (e.g., in a subcutaneouspocket over the hip or in the subclavicular area). In one embodiment,the electrode lead 12 used in the screening test and/or home-trial maybe totally removed and discarded, and a new completely implantable leadmay be tunneled subcutaneously and coupled to the implantable pulsegenerator. In an alternative embodiment, a two part lead may beincorporated in the screening test and/or home-trial where theimplantable part is completely under the skin and connected to apercutaneous connector (i.e., extension) that can be discarded afterremoval. The implantable part may then be tunneled and coupled to theimplantable pulse generator, or a new sterile extension may be used tocouple the lead to the implantable pulse generator.

Alternatively, when the targeted nerve of passage includes one or morenerves of the lumbar plexus or sacral plexus, the approach may be eithera posterior (shown in FIG. 16A) or an anterior approach (shown in FIG.17A), similar to those used for regional anesthesia of the same targetednerve of passage, except that the approach is used for placement throughan introducer of stimulation lead(s) or electrode (s) in electricalproximity to but spaced away from a nerve of passage, and not forchemically-induced regional anesthesia. Unlike regional anesthesia, theapproach to nerves of the lumbar plexus or sacral plexus do not involvethe application of anesthesia to the nerve, and, when the introducer iswithdrawn, the lead(s) or electrode(s) may be left behind to provide thedesired stimulation of the target nerve of passage.

For example, when the targeted nerve of passage includes the sciaticnerve (see FIG. 18A), the introducer(s) 30 and/or lead(s) 12 may bedirected towards the sciatic nerve using a posterior approach, such asthe transgluteal approach or subgluteal approach, which are both welldescribed and commonly used in regional anesthesiology (Dalens et al.1990; Bruelle et al. 1994; di Benedetto et al. 2001; Gaertner et al.2007)

Alternatively, an adapted approach may also be used which is similar toapproaches used in regional anesthesiology but may be adapted tominimize patient discomfort or damages or complications related to thetherapy and/or system. As an example, the introducer(s) and/or lead (s)may be inserted from a more lateral insertion site (or another site thatis more desirable) than is typically used for regional anesthesiologybecause it has been found that a more lateral (or other) insertion siteminimizes patient discomfort. The insertion site and/or path may beadapted or an alternative insertion site and/or path may be selectedwith an understanding of the type of tissue, muscle and other tissueplanes, compartments, innervation of the tissue, muscle orientation,muscle fiber directionality, vascular and/or lymphatic vessels andstructures, and other considerations below, surrounding, or near theinsertion site or path. As non-limiting examples, it may be desirable tominimize the number of muscle planes that are transversed or crossedwith the introducer(s) and/or lead(s), or it may be desirable to use aninsertion site and/or insertion path that is not densely innervated bynon-target sensory nerve fibers, maximizing the comfort of the placementprocedure and the therapy following removal of the introducer, or it maybe desirable to orient the direction of the introducer(s) and/or lead(s)relative to the directionality of the muscle fibers, placing the lead(s)in line with (e.g. parallel to) or orthogonal to the muscle fibers orany variation between parallel or orthogonal to the muscle fibers.

This approach allows lead placement near a targeted nerve of passagewith a simple, quick (e.g. less than 10 minutes) outpatient procedurethat may be performed in a standard community-based clinic. This makespossible widespread use and provides a minimally-invasive screening testto determine if patients will benefit from the device before receiving afully implanted system.

The landmarks for the transgluteal approach may include the greatertrochanter and the posterior superior iliac spine. The introducer 30 maybe inserted distal or proximal (e.g. approximately up to about 12 cm ina preferred embodiment) and/or medial or lateral (e.g. approximately upto about 12 cm in a preferred embodiment) to the midpoint between thegreater trochanter and the posterior iliac spine. Alternatively, theintroducer 30 may be inserted at the midpoint between the greatertrochanter and the posterior iliac spine. As a non-limiting example ofpatient positioning, the patient may be in a lateral decubitus positionand tilted slightly forward in a preferred embodiment.

The landmarks for the subgluteal approach may include the greatertrochanter and the ischial tuberosity. The introducer may be inserteddistal or proximal (e.g. approximately up to about 12 cm in a preferredembodiment) and/or medialorlateral (e.g. approximately up to about 12 cmin a preferred embodiment) to the midpoint between the greatertrochanter and the ischial tuberosity. Alternatively, the introducer 30may be inserted at the midpoint between the greater trochanter and theischial tuberosity.

For any approach targeting the sciatic nerve (e.g. the transgluteal,subgluteal, and/or another or adapted approach), it may be beneficial toinsert the introducer lateral to the midpoint between the relevantlandmarks. A more lateral insertion point may maximize safety to thepatient and/or the system, and it may increase patient comfort andminimize risk of damage to the lead or migration of the lead. As anon-limiting example of lateral placement, the introducer may beinserted lateral to the midpoint between the greater trochanter and theischial tuberosity. The introducer may be inserted anywhere between themidpoint and the greater trochanter. The introducer may be insertedproximal or distal to the line between the greater trochanter andischial tuberosity. It may be beneficial to insert the introducer distalto this line.

For example, when the targeted nerve of passage includes the femoralnerve (see FIG. 18A), percutaneous leads 12 may be directed towards thefemoral nerve using an anterior approach. The landmarks may include theinguinal ligament, inguinal crease, and femoral artery. The patient maybe in the supine position with ipsilateral extremity slightly(approximately 10 to 20 degrees) abducted. The introducer may beinserted near or below the femoral or inguinal crease and approximately1 cm or more lateral to the pulse of the femoral artery. More detail onplacement of a percutaneous lead 12 for stimulation of the femoral nervemay be found below.

The size and shape of tissues, such as the buttocks, surrounding thetarget nerves may vary across patients, and the approach may be modifiedas needed to accommodate various body sizes and shapes to access thetarget nerve.

In non-amputee patients, introducer placement can be often guided bymuscle response to electrical stimulation, but the muscle response maynot be available in amputees, or may not be available and/or beunreliable in other situations (e.g., a degenerative diseases orcondition such as diabetes of impaired vascular function in which thenerves are slowly degenerating, progressing from the periphery, or dueto trauma).

In these situations, placement may be guided by the individual's reportof stimulus-evoked sensations (paresthesias) as the introducer is placedduring test stimulation. Additionally, the response of remaining musclesto stimulation may also be used to guide placement of the introducer andelectrode.

As shown in FIG. 18B, more than a single lead 12 may be placed around orin the vicinity of a given nerve of passage, using either an anteriorapproach (e.g., femoral nerve) or a posterior approach (e.g., sciaticnerve). As FIGS. 19A, B, and C show, one or more leads 12 can be placedat different superior-inferior positions along a nerve of passage and/oralong different nerves of passage.

As FIGS. 16B (anterior approach, e.g., femoral nerve) and 17B (posteriorapproach, e.g., sciatic nerve) show, the lead 12 can be coupled to anexternal pulse generator 28 worn, e.g., on a belt 52, for a trial ortemporary stimulation regime. In this arrangement, the lead 12 iscovered with a bandage 50, and a surface electrode 54 serves as a returnelectrode. The external/percutaneous system shown in FIGS. 16B and 17Bmay be replaced by an implanted system using an implanted pulsegenerator 60 and intramuscular and/or adipose and tunneled leads 62, asshown in FIGS. 16C and 17C, respectively. In this arrangement, the caseof the implanted pulse generator 60A comprises the return electrode.

D. Stimulation Parameters

Control of the stimulator and stimulation parameters may be provided byone or more external controllers. In the case of an external stimulator,the controller may be integrated with the external stimulator. Theimplanted pulse generator external controller (i.e., clinicalprogrammer) may be a remote unit that uses RF (Radio Frequency) wirelesstelemetry communications (rather than an inductively coupled telemetry)to control the implanted pulse generator. The external or implantablepulse generator may use passive charge recovery to generate thestimulation waveform, regulated voltage (e.g., 10 mV to 20 V), and/orregulated current (e.g., about 10 μA to about 50 mA). Passive chargerecovery is one method of generating a biphasic, charge-balanced pulseas desired for tissue stimulation without severe side effects due to aDC component of the current.

The neurostimulation pulse may by monophasic, biphasic, and/ormulti-phasic. In the case of the biphasic or multi-phasic pulse, thepulse may be symmetrical or asymmetrical. Its shape may be rectangularor exponential or a combination of rectangular and exponentialwaveforms. The pulse width of each phase may range between e.g., about0.1 μsec. to about 1.0 sec., as non-limiting examples. The preferredneurostimulation waveform is cathodic stimulation (though anodic willwork), biphasic, and asymmetrical.

Pulses may be applied in continuous or intermittent trains (i.e., thestimulus frequency changes as a function of time). In the case ofintermittent pulses, the on/off duty cycle of pulses may be symmetricalor asymmetrical, and the duty cycle may be regular and repeatable fromone intermittent burst to the next or the duty cycle of each set ofbursts may vary in a random (or pseudo random) fashion. Varying thestimulus frequency and/or duty cycle may assist in warding offhabituation because of the stimulus modulation.

The stimulating frequency may range from e.g., about 1 Hz to about 300Hz, and the frequency of stimulation may be constant or varying. In thecase of applying stimulation with varying frequencies, the frequenciesmay vary in a consistent and repeatable pattern or in a random (orpseudo random) fashion or a combination of repeatable and randompatterns.

In a representative embodiment, the stimulator is set to an intensity(e.g. 0.1-20 mA (or 0.05-40 mA, or 0.01-200 mA), a pulse duration orwidth 1-300 μs (or 5-1000 μs, or 1-10,000 μs)) sufficient to activatethe targeted nerve of passage at some therapeutically effective distance(e.g. 1 mm or more) away (from the targeted nerve of passage). If thestimulus intensity is too great, it may generate muscle twitch (es) orcontraction(s) sufficient to disrupt correct placement of the lead. Ifstimulus intensity is too low, the lead may be advanced too close to thetargeted nerve of passage (beyond the optimal position), possiblyleading to incorrect guidance, nerve damage, mechanically evokedsensation (e.g. pain and/or paresthesia) and/or muscle contraction (i.e.when the lead touches the nerve of passage), inability to activate thetarget nerve fiber(s)

without activating non-target nerve fiber(s), improper placement, and/orimproper anchoring of the lead (e.g. the lead may be too close to thenerve and no longer able to anchor appropriately in the muscle tissue).

In a representative embodiment, the stimulator is set to a frequency(e.g. 0.5-12 Hz (or 0.1-20 Hz, or 0.05-40 Hz)) low enough to evokevisible muscle twitches (i.e. non-fused muscle contraction) and/ormuscle contraction (s) of the targeted muscle (s) innervated by thetarget nerve of passage, but high enough that that the targeted nerve ofpassage will be activated before the lead is advanced beyond the optimalposition.

As an alternative to using muscle twitch (es) or contraction (s) asindicator (s) of lead placement (distance from the nerve of passage toelectrode contact), patient sensation could instead be used to indicatelead location relative to the targeted nerve of passage. Any combinationof stimulus parameters that evoke sensation(s) may be used. Somestimulus parameters may evoke a more desirable response (e.g. morecomfortable sensation, or a sensation that may be correlated with orspecific to the specific target nerve fiber (s) within the targetednerve of passage. As an example, higher frequencies (e.g. 12 Hz, or 4Hz, or 0.1 Hz) may evoke sensation(s) or comfortable paresthesia(s) inthe region(s) of pain or in alternate target region (s) (real orphantom) and though they may (or may not) also evoke musclecontraction(s), the muscle contraction(s) may not be noticeable (e.g.stimulus intensity may not be sufficient to evoke a contraction or atwitch from the present lead location or stimulus intensity may besufficient to evoke contraction but the muscle contraction is fused (andno longer visually twitching), making it difficult to observe visually,unless EMG is used). To take advantage of both potential indicatorresponses (muscle twitch and patient sensation), higher frequencies maybe applied intermittently (at lower frequencies), where the higherfrequencies (e.g. 20-120 Hz, or 12-200 Hz) would normally caused fusedmuscle contraction if they were applied continuously but they areapplied at an intermittent frequency (e.g. 0.5-4 Hz, or 0.1-11 Hz) thatis low enough to allow the muscle to relax during the gaps between thebursts of stimulation, making it easier to visualize while stillgenerating patient sensation at a higher frequency, allowing both muscletwitch and patient sensation to be used simultaneously as indicators oflead location relative to the targeted nerve of passage.

While stimulation is being applied, the lead (non-limiting examples ofthe lead could include a single or multi-contact electrode that isdesigned for temporary (percutaneous) or long-term (implant) use or aneedle electrode (used for in-office testing only)) may be advanced(e.g. slowly advanced) towards the targeted nerve of passage until thedesired indicator response (e.g. muscle twitch, muscle contraction,patient sensation, and/or some combination) is obtained at a firstlocation X1. The intensity may then be decreased (e.g. graduallydecreased) as the lead is advanced (e.g. advanced slowly) closer to thetargeted nerve of passage until the desired indicator response(s) may beobtained at smaller intensity(ies) within the target range (e.g. 0.1-20mA (or 0.09-39 mA, or 0.009-199 mA), 1-300 μs (or 5-1000 μs, or 1-10,000μs)) at some distance (e.g. X2 mm, where X2<X1, and (as a non-limitingexample) X1 may be multiple times larger than X2, such as X1 2*X2, or X15*X2, or X1 20*X2 from the target nerve. If specific response (s) (e.g.desired response (s) and/or undesired response (s)) can be obtained at arange of intensities that are too low, then the lead may be located in anon-optimal location (e.g. too close to the target nerve (s))Non-limiting examples of ranges of intensities that may be consideredtoo low include those that are a fraction (e.g. <⅔, or <⅕, or < 1/10) ofthe intensities that obtained the desired response(s) at X1.

Additionally or alternatively, preferably with stimulation turned off, aneedle electrode (e.g., an EMG monitoring electrode connected to astimulator) may be inserted a predetermined distance, such asapproximately to about 5.0 centimeters, and more preferably 0.5 to about3.0 centimeters, from a target neural structure. The initial placementis preferably confirmed by the use of ultrasound imaging, includingbiological landmark identification. Such landmarks may include one ormore of the femoral vein and/or femoral artery. Once inserted to aninitial position, a test stimulation may be delivered by the needleelectrode at a desired intensity (e.g., a pulse duration or width ofabout 5 to about 50 μs, a frequency of about 4 to about 200 Hz, and anamplitude of about 0.1 mA delivered constantly). If no neurologicalresponse is reported by the patient and no neurological response isobserved or detected by the clinician, the amplitude of the teststimulation may be increased until a neurological response is reported,observed, or detected. A neurological response may be reported,observed, or detected at a location that is local to the stimulationdelivery location (e.g. near the needle electrode). If a sensation isreported by the patient or a muscle contraction is observed at suchlocation, the needle electrode may be too superficial and the electrodemay be advanced further towards the target neural structure. In thiscase, the electrode is preferably advanced while the stimulation isturned off. Advancement may occur in the range of 0.1-2 cm, and the teststimulation process may be repeated. If a sensation is reported by thepatient and the sensation is an uncomfortable sensation perceived to beoriginating at a point distal to the location of the electrode, or if aneurological response of muscle contraction is observed or detected asoccurring distal to the electrode, it is an indication that the needleelectrode is too close to the target neural structure, and the electrodeis slightly withdrawn in the range of 0.1-2 cm while maintaining theneedle electrode in vivo. During this slight withdrawal of theelectrode, the stimulation is preferably off, and the test stimulationprocess may be repeated after electrode relocation. If in vivoreadjustment or relocation of the electrode does not result in the goalof comfortable paresthesia in an area of pain, the needle electrodeinsertion trajectory and/or insertion site may be adjusted and theprocess repeated. Once an appropriate electrode location has beendetermined, the depth and trajectory is noted and used for guidingand/or informing the insertion of the treatment stimulation electrode tobe anchored for a predetermined treatment duration.

The preferred stimulus intensities are a function of many variables, aremeant to serve as non-limiting examples only, and may need to be scaledaccordingly. As an example, if electrode shape, geometry, or surfacearea were to change, then the stimulus intensities may need to changeappropriately. For example, if the intensities were calculated for alead with an electrode surface area of approximately 20 mm², then theymay need to be scaled down accordingly to be used with a lead with anelectrode surface area of 0.2 mm² because a decrease in stimulatingsurface area may increase the current density, increasing the potentialto activate excitable tissue (e.g. target and non-target nerve(s) and/orfiber(s)). Alternatively, if the intensities were calculated for a leadwith an electrode surface area of approximately 0.2 mm², then theintensities may need to be scaled up accordingly to be used with a leadwith an electrode surface area of 20 mm². Alternatively, stimulusintensities may need to be scaled to account for variations in electrodeshape or geometry (between or among electrodes) to compensate for anyresulting variations in current density. In a non-limiting example, theelectrode contact surface area may be 0.1-20 mm², 0.01-40 mm², or0.001-200 mm². In a non-limiting example, the electrode contactconfiguration may include one or more of the following characteristics:cylindrical, conical, spherical, hemispherical, circular, triangular,trapezoidal, raised (or elevated), depressed (or recessed), flat, and/orborders and/or contours that are continuous, intermittent (orinterrupted), and/or undulating.

Stimulus intensities may need to be scaled to account for biologicalfactors, including but not limited to patient body size, weight, mass,habitus, age, and/or neurological condition (s). As a non-limitingexample, patients that are older, have a higher body-mass index (BMI),and/or neuropathy (e.g. due to diabetes) may need to have stimulusintensities scaled higher (or lower) accordingly.

As mentioned above, if the lead is too far away from the targeted nerveof passage, then stimulation may be unable to evoke the desired response(e.g. muscle contraction(s), comfortable sensation(s) (orparesthesia(s)), and/or pain relief) in the desired region(s) at thedesired stimulus intensity(ies). If the lead is too close to thetargeted nerve of passage, then stimulation may be unable to evoke thedesired response(s) (e.g. muscle contraction(s), comfortable sensation(s) (or paresthesia (s)), and/or pain relief) in the desired region(s)at the desired stimulus intensity (ies) without evoking undesirableresponse (s) (e.g. unwanted and/or painful muscle contraction(s),sensation(s) (or paresthesia(s)), increase in pain, and/or generation ofadditional pain in related or unrelated area (s)) In some cases, it maydifficult to locate the optimal lead placement (or distance from thetargeted nerve of passage and/or it may be desirable to increase therange stimulus intensities that evoke the desired response (s) withoutevoking the undesired response(s) so alternative stimulus waveformsand/or combinations of leads and/or electrode contacts may be used. Anon-limiting example of alternative stimulus waveforms may include theuse of a pre-pulse to increase the excitability of the target fiber(s)and/or decrease the excitability of the non-target fiber(s).

Those skilled in the art will recognize that, for simplicity andclarity, the full structure and operation of all devices and processessuitable for use with the present invention is not being depicted ordescribed herein. Instead, only so much of an implantable pulsegenerator and supporting hardware as is unique to the present inventionor necessary for an understanding of the present invention is depictedand described. The remainder of the construction and operation of theIPGs described herein may conform to any of the various currentimplementations and practices known in the art.

III. Representative Indications for Chronic or Temporary Pain Therapy

Localized pain in any area of the body (e.g., the skin, bone, joint, ormuscle) can be treated by applying electrical stimulation to tissue(e.g. muscle, adipose, connective or other tissue) in electrical contactwith but spaced from a targeted nerve of passage. Electrical stimulationof nerves of passage works by interfering with or blocking pain signalsfrom reaching the brain, as FIG. 10 schematically shows.

Many pain indications can be treated by nerves of passage stimulation.

Pain in the leg may occur in areas such as the thigh, calf, hip, shin,knee, foot, ankle, and toes. There may be multiple causes of leg pain,including but not limited to injury (e.g. traumatic) to a muscle, joint,tendon, ligament or bone; muscle or ligament damage; ligament sprain,muscle or tendon strain; disease or disorders; phlebitis, swelling, orinflammation; claudication; insufficient blood flow into (arterialinsufficiency) or away from (venous insufficiency) a part of the leg orfoot; ischemia; peripheral artery disease; arthritis; tumor (malignantor benign); peripheral neuropathy; diabetic peripheral neuropathy; andpost herpetic neuralgia.

For example, peripheral artery disease can cause pain (especially duringactivity such as walking or running) because the effective narrowing ofthe arteries leads to a decrease in the supply of blood and therefore inthe supply of nutrients such as oxygen to the active muscles, leading topain. This phenomenon can occur in almost in area of the body but may bemore common in the leg, especially parts of the lower leg, such as thecalf. Activity is not always required to elicit pain and pain may occureven at rest (without activity or exercise). Nerve entrapment,compression, injury or other types of damage may cause pain in the areasinnervated by the damaged nerve, which can lead to referred pain in anarea distal to the injury.

For example, claudication pain (occurring in the calf muscle) could betreated by nerves of passage stimulation by placing the lead in thegluteus muscle near the sciatic nerve, which passes by the gluteusmuscle on its way to innervate the calf muscle.

In general pain due to poor blood flow to an area or damage to an areacan be relieved by stimulation of the nerve innervating that area. Sincediabetic neuropathy typically leads to pain in the more distal areas(toes/foot), stimulation of the sciatic nerve can relive that pain. Painin the skin of the medial (inner) calf can be relieved by stimulation ofthe femoral nerve. Pain in the front of the thigh (quad's) can berelieved by stimulation of the femoral nerve. If pain overlaps more thanone area, stimulation of multiple nerves (e.g., sciatic and femoralnerves) can be beneficial.

Stimulation of the intercostal nerves (originating from the Thoracicnerve roots (T1-12)) can relieve pain in regions innervated by theintercostal nerves such as pain from intercostal neuralgia or postherpetic neuralgia. The pain may be confined to the area (e.g.dermatomic area) innervated by 1 or 2 nerves and may follow outbreak(and recovery) of herpes zoster. The pain may last up to several monthsor years in some patients and may be caused by nerve irritation ordamage due to herpes zoster.

Post-amputation (e.g. including residual limb and/or phantom limb) paincan also be treated by nerves of passage stimulation. For example, upperextremity stimulation of spinal nerves passing through the brachialplexus can relive residual limb pain and/or phantom limb pain thatresults from amputation of an upper limb. Likewise, lower extremitystimulation of spinal nerves passing through the lumber plexus sacralplexus (e.g., the sciatic nerve or the femoral nerve) can reliveresidual limb pain and/or phantom limb pain that results from amputationof a lower limb.

In one case study performed according to the present invention, in thetreatment of post-amputation pain, the patient was a 49 year oldAfrican-American male who complained of severe residual limb pain (RLP)secondary to a below-the-knee amputation of his right leg (900 in FIGS.23A and 23B) following a motor vehicle accident 33 years prior toenrollment into the study. The patient reported that the RLP remainedsevere despite a history of using narcotic analgesics, anticonvulsants,non-steroidal anti-inflammatory drugs (NSAIDs), physical therapy, andnerve blocks.

Inclusion criteria for enrollment in the case study included a wellhealed unilateral lower extremity amputation, residual limb pain and/orphantom limb pain score 4 on an 11-point numerical rating scale on theBrief Pain Inventory-Short Form (BPI-SF) Question #3 (BPI3), BeckDepression Inventory (BDI) score of 20 and age 18 years. Exclusioncriteria included the absence of sepsis, infection; diabetes mellitustype I and II, implanted electronic devices, anticoagulation therapy(aside from aspirin therapy), history of valvular heart disease,pregnancy and any previous allergy to skin contact materials and oranesthetic agents. Also consistent with the exclusion criteria, thepatient had not had a botulinum toxin injection within the last 6 monthsin the affected limb, had not had a steroid injection within the last 6weeks in the affected limb, and had not participated in any drug ordevice trial in the past 30 days.

The patient was provided with a diary and asked to record medicationusage and worst-pain levels every day for the duration of the 8-weekstudy. Throughout the study, the patient reported taking the followingmedications daily: one multivitamin (1 time/day), ibuprofen (800 mg, 3times/day), and gabapentin (600 800 mg, 3 times/day) At the end of a2-week baseline period, the patient requested that his dose ofgabapentin be increased from 600 mg to 800 mg in response to a recentback injury unrelated to the study. The patient continued to take the800 mg dose of gabapentin for the remaining 6 weeks of the study.

After completing the 2-week baseline period, the patient returned forelectrical stimulation lead placement and electrical stimulation testing(Visit 2). The electrical lead was a fine-wire helical coil wound from aseven-strand, type 316L stainless steel wire with a single anchoringbarb and a single electrode contact, such as that shown in FIG. 20 .

Turning now to FIG. 20 , a preferred percutaneous lead 400 may bedescribed. This lead 400 is a suitable lead 12 to be used as describedherein. The lead 400 preferably includes an electrode 402 that extendsfrom preferably an insulated conductor 404 having an insulated diameter406 of about 10 mils. The insulated conductor 404 is preferably 4250 PFAcoated 7-strand 316L stainless steel, which is preferably wound about amandrel to form an insulated coiled portion 408 of a desired length,such as about seven to about nine inches. A portion of a distal end ofthe conductor 404 is stripped to form the electrode 402. The strippedportion is preferably coiled on a mandrel to an outside diameter ofabout 10 mils to about 15 mils, and then bent at an electrode angle 410of about 20 degrees to about 70 degrees. The electrode 402 includes anextension 412 and a barb 414. The extension 412 has an electrodeextension length 416 of about 350 mils to about 450 mils, and the barb414 has a barb length 418 of about half that of the extension length416, of about 160 mils to about 240 mils. At the juncture of theelectrode 402 and the coiled insulated portion 408, a fillet of siliconadhesive 419, such as Nusil Med 1511, is preferably providedcircumferentially about the lead 400. A test portion 420 of a proximalend of the lead 400 may also be stripped and tinned, and a maximumend-to-end resistance of the lead 400 is preferably about 150 ohms.Provided at a tip 422 of the barb 414 of the electrode 402 is preferablya weld to maintain the conductors of the lead 400 in a desired position.An electrically conductive path in which the lead 400 is used preferablyhas a maximum resistance of about 1300 ohms.

The lead 400 described may be used percutaneously, i.e. introduced andoperatively extending through the epidermis of an animal, thus providingan insulated, electrically conductive path through such epidermis. Toaccomplish such introduction, a lead introducer 700 may be used, such asthat shown in FIGS. 21-22 . This introducer 700 is a suitable introducer30 to be used as described herein. The introducer 700 extends from aproximal end 702 to a distal end 704, with a lumen 706 extendingtherethrough. Provided at the proximal end 702 may be preferably alocking Luer hub 706, which may be electroless nickel plated brass 360having a Luer taper conforming to ISO 594-1:1986. Extending from the hub706 towards the distal end 704 is an introducer needle 708 made from 20gauge 304 full hard stainless steel thin wall hypodermic tubing with anoutside diameter of about 35 to about 36 mils and an inside diameter ofabout 25 to about 30 mils. The Luer hub 706 and needle 708 arepreferably coated with 0.1 to mils of electrically insulative SCSParylene C conformal coating applied to external surfaces. Theelectrically insulative coating preferably provides at least 100 voltminimum dielectric strength. A plurality of depth markings 710 arepreferably provided along the length of the needle 708. Preferably,twelve such markings 710 are provided at a spacing of about 400 mils.The markings 710 may be formed, e.g., by laser etching.

At the distal end 704, the needle 708 is preferably ground to athree-face lancet formation, including a point 712, a bevel portion 714,and a non-coring heel portion 716. The cuts to form the bevel 714 andheel portion 716 are all preferably provided at an angle of about 18degrees from longitudinal parallels to the exterior surface of theneedle 708.

The lead was insulated with perfluoroalkoxy and preloaded in a 20 gauge,insulated hypodermic needle introducer. During Visit 2, the patient wasplaced in a supine position to allow access to the femoral nerve usingan anterior approach. The insertion site was cleansed using aseptictechnique and local anesthesia was administered.

Prior to placing the fine-wire lead, a monopolar needle electrode 800(24 gauge, Jari Electrode Supply, Gilroy, Calif.) was inserted below thefemoral (or inguinal) crease and lateral (as opposed to medial) to theright femoral artery to within about 0.5 centimeters to about 1centimeter of the femoral nerve under ultrasound guidance 805,preferably prior to delivering test stimulation. (See FIG. 23A.) Theinsertion site can be at the level of the inguinal (or femoral) crease902 or it could be above or below it. While a preferred insertion sitemay be a few centimeters (1-5 cm, but typically no more than 10 cm) ineither direction, good results may still be obtained if the insertionsite is more than 10 cm away from the crease 902. The location of thenearby blood vessels (femoral artery 904 & vein) may also be used aslandmarks, and the lead is typically inserted lateral (some distance,typically 1 mm to approximately 5 cm, but usually no more than 10 cm) tothe femoral artery. The artery can be visualized on ultrasound and/orlocated by palpating (feeling) the pulse. Although the insertion sitemay be placed on either (lateral or medial) side of the femoral nerve ordirectly above (superficial to) the nerve (or the artery or vein), theinsertion site (and the electrode) is preferably positioned lateral tothe artery to minimize the risk of puncturing a blood vessel.

Test stimulation (40 μs, 1 mA, 50 Hz) was delivered with aregulated-current stimulator (Maxima II, Empi, Inc., St. Paul, Minn.) toconfirm that the angle of insertion 810 (about from skin surface) andthe length of needle under the skin (about 3.6 centimeters) wassufficient to evoke a comfortable paresthesia in a region of paininnervated by the femoral nerve. The angle of insertion may be less thanor greater than the 40 degrees used in this study. Where greater lateralresolution is desired, that is, where fine lateral adjustment isdesirable, lower angles of insertion may be utilized such that lesslateral electrode translation occurs for a given longitudinal movementof the percutaneous lead. For instance, while a 90-degree entry anglewould correspond to a 1:1 lateral translation of the electrode duringlead movement (e.g. 1 mm lateral electrode translation would require 1mm longitudinal lead movement), a 15-degree entry angle would correspondto approximately a 1:4 lateral translation (e.g. 1 mm lateral electrodetranslation would require 4 mm longitudinal lead movement). Steeperinsertion angles may be required if a target nerve is less superficialand shallower insertion angles may be used if the target nerve is moresuperficial. One goal may be to have the electrode disposed in thevicinity of the femoral nerve near its trunk (cranial to the portionwhere it begins to fan out & separate into multiple branches). However,it may be acceptable if the electrode is disposed in another location(e.g. below the point where the nerve has begun to fan out into multiplebranches), sufficient activation of the target fibers within the nervecan still be obtained even if the electrode placement is not ideal.

Another advantage to a more shallow insertion angle is that it can allowmore of the lead to be located under the skin (near shallow nerves, suchas the femoral nerve), increasing its ability to resist unwantedmovement, dislodgement, and migration. A shallow angle of insertioncapitalizes on these mechanical advantages without compromising theelectrical advantages of this approach (to activate selectively thetarget fibers for pain relief without generating unwanted or noxioussensations (such as pain, discomfort) or unwanted muscle contraction).The shallow angle is less critical when the target nerve is locateddeeper under the skin, such as with the sciatic nerve. In the case ofthe sciatic nerve, it may be preferable to use a more perpendicularangle (even 90 degrees).

While it is preferred that the electrode and/or lead are disposed almostparallel to the femoral artery, good results can be obtained even if theelectrode and/or lead are not so oriented; however, the closer toparallel (& the less perpendicular) to the artery the direction ofneedle insertion, there exists less risk of puncturing a blood vessel.That said, a slightly non-parallel (relative to the nerve) insertionangle could be advantageous in some circumstances becauseadvancement/withdrawal of the electrode (along the length/direction ofthe introducer) will bring the electrode closer to/farther away from thenerve and/or where precise placement along the length of a nerve isdesired or required.

The monopolar needle electrode was withdrawn and replaced with thefine-wire lead 400 using at least substantially the same insertion siteand at least substantially the same approach except that the introducerwas inserted a shorter distance than the test stimulation needleelectrode was, preferably about two centimeters under the skin, placingthe electrode a remote distance 820 (more than 1 centimeter away) fromthe nerve. (See FIGS. 23B and 24 .)

Correct lead placement was confirmed by evoking a comfortableparesthesia with stimulation (50 μs, 1 mA, 50 Hz) that covered 75% ofthe painful area without evoking muscle contractions, qualifying thepatient to proceed to the 2-week home trial. The stimulator was replacedwith a regulated-voltage stimulator (Rehabilicare NT2000, Empi, Inc.,St. Paul, Minn.). Stimulation pulse width was set (30 μs) and amplitudewas increased to evoke the maximum comfortable paresthesia coverage(75%). The lead was deployed by withdrawing the introducer needle whilemaintaining pressure at the skin surface. A portion of the lead wascoiled outside the skin to create a strain-relief loop, and the exitsite was bandaged with waterproof bandages (Tegaderm by 3M, St. Paul,Minn.). The patient was instructed on the use of the stimulator and careof the bandages before progressing to the first week of the home trial.

The patient returned as planned (Visit 3) to the clinic after the firstweek of the home trial for bandage change, exit site inspection, and asmall increase in stimulus pulse width from 30 μs to 40 μs. The patientreported improved comfort in response to the change in pulse width, andthe patient progressed to the second week of the home trial.

The patient returned as planned after the second week of the home trialfor lead removal (Visit 4), and again for the 1-week (Visit 5) and4-week (Visit 6) follow-up visits after lead removal.

During lead placement (Visit 2) and the following 2-week home trial, thepatient reported comfortable paresthesia coverage of greater than orequal to 50% (e.g. greater than or equal to 75%) of the region ofresidual limb pan (RLP), and no muscle contractions were observed inresponse to electrical stimulation.

Electrical stimulation of the femoral nerve reduced the RLP of thepatient by 60% from baseline by the end of the 2-week home trial (seeFIG. 25 ). The 3-day average of the BPI3 (daily worst pain) score duringbaseline was 7.7 prior to stimulation. This same score decreased to 3.7after the first week of stimulation, and further decreased to 3 by theend of the second week of stimulation. Following the end of stimulationand lead removal, pain returned within 24 hours to a BPI3 score of 6remained at approximately this level for the duration of the 4-weekfollow up.

The sum of the pain interference scores for the Brief PainInventory-Short Form (BPI-SF) decreased from at baseline to 12 (71%improvement) after the first week of stimulation and to 0 (100%improvement) after the second week of stimulation (see FIG. 26 ).Following the end of stimulation and lead removal, the pain interferencescores increased to 10 (76% change from baseline) at the 1-weekfollow-up visit and to 13 (69% change from baseline) at the 4-weekfollow-up visit.

At baseline, the sum of the Pain Disability Index (PDI) scores was 42,which decreased to 23 (45% improvement) after the first week ofstimulation and further decreased to 11 (74% improvement) after thesecond week of stimulation. Following the end of stimulation and leadremoval, the sum of the PDI scores remained at 11 at the 1-weekfollow-up visit and increased to 20 (53% change from baseline) at the4-week follow-up visit.

The sum of scores on the Beck Depression Inventory (BDI-II) was 0 atbaseline and at the end of the 2-week stimulation home trial. The scorefluctuated by 1 point (3% of the total possible score) during the othervisits. Relative to baseline, the patient reported on the Patient GlobalImpression of Change (PGIC) scale that he felt “Much Improved” after thefirst week of stimulation and “Very Much Improved” after the second weekof stimulation. Following the end of stimulation and lead removal, thepatient reported feeling “Much Improved” at the 1-week follow-up visitand “Minimally Improved” at the 4-week follow-up visit.

The patient reported no phantom limb pain throughout the study with theexception of one diary entry on a single day during the baseline period.The lead was removed, intact, during Visit 4, and no adverse events werereported.

The present implementation demonstrates the first time peripheral nervestimulation (PNS) has generated clinically significant relief ofpost-amputation pain using a lead placed percutaneously a remotedistance away from a nerve. During the 2-week home trial of stimulation,60% improvement was observed in the BPI3 (worst daily pain), whichtranslated into a reduction in pain classification from severe pain(score 7) to minor pain (score 3) and correlated with similarimprovements in quality of life measures.

The 2-week home trial produced complete resolution (100%) of theinterference of pain on daily activities and moods as measured by theBrief Pain Inventory-Short Form (BPI-SF), and it greatly reduced (74%)the impact of pain on physical functioning and activities of dailyliving as measured by the Pain Disability Index (PDI). Emotionalfunctioning was not impaired by pain at baseline, and it did not changesignificantly throughout the study as measured by the Beck DepressionInventory (BDI-II) The patient reported that his overall quality of life(activity limitations, symptoms, and emotions) related to his pain was“Very much improved” (the maximum score possible) by the end of the2-week home trial relative to baseline as measured by the Patient GlobalImpression of Change (PGIC).

The method of PNS used in the present study is distinct from peripheralnerve field stimulation or subcutaneous stimulation in which the lead isplaced in the region of pain to activate nearby nerve branches andprovide pain relief to the local surrounding area. In contrast to suchprior methods, in the present study, the lead was placed outside of thearea of pain to activate the femoral nerve trunk and provide relief todistal areas of pain, or areas perceived to be experiencing pain thatare located more distally from the central nervous system than thelocation of the nerve trunk activation. The present study complementsprevious studies of spinal cord stimulation and peripheral nervestimulation (PNS) that indicate electrical stimulation has the potentialto provide significant relief of post-amputation pain when stimulationgenerates >50% paresthesia coverage of the painful region. Contrary toprior studies, in the present study, the patient reported 75%paresthesia coverage and >60% pain relief during the 2-week trial.

PNS offers the potential to deliver therapeutic stimulation to the nerveinnervating the region of pain and limit the distribution of paresthesiato the area in which it is needed. However, PNS has not generally beenused to treat post-amputation pain because conventional knowledgeindicated that presently available PNS systems can be technicallychallenging to place in close proximity to the nerve. Traditionally,electrical stimulation of a large peripheral nerve trunk, such as thefemoral nerve, has required surgical access and dissection to place acuff-, paddle-, or plate-style lead in intimate contact with the nerve.However, recent studies have shown that cylindrical leads can be placedpercutaneously in close proximity (2 mm) thought to be required foradequate efficacy, to the nerve under ultrasound guidance. The presentinvention builds on prior methodologies by demonstrating that astimulation electrode may be placed percutaneously and remotely (>1 cmaway) from a nerve and still obtain significant paresthesia coverage andpain relief.

The ability to generate significant paresthesia coverage and pain reliefwith a single lead, and indeed a single electrode even, insertedpercutaneously and disposed remotely from a target nerve holds promisefor providing relief of post-amputation pain.

Case Series

In addition to the study described above, an additional study includingmultiple patients has been conducted to determine, among other things,whether surgical access could be avoided by inserting a single-contactlead remote (0.5-3 cm away) from the large nerve trunks.

This further study was a case series of lower-extremity amputees withmoderate to severe post-amputation pain. Residual limb pain (RLP) andphantom limb pain (PLP) were measured and assessed independently on a0-10 scale for each individual. A fine-wire lead was insertedpercutaneously under ultrasound guidance to within 0.5-J cm of thesciatic and/or femoral nerve trunks. Correct lead placement wasconfirmed by evoking a comfortable paresthesia that covered >50% of thepainful area without evoking muscle contractions, qualifying theindividual to proceed to a 2-week home trial of stimulation, prior towhich the individual was instructed on how to maintain a diary of theirrespective pain levels. For instance, the individual was instructed torecord maximum pain levels every day, preferably at approximately thesame time each day. For instance, for patients with RLP, the patient wasinstructed to record, on a scale of 0-10 where 0 indicates no pain and10 indicates a level of pain as bad as the individual can imagine, hisor her maximum amount of residual limb pain typically felt over the past24 hours. For patients with PLP, the patient was instructed to record,on a scale of 0-10 where 0 indicates no pain and 10 indicates a level ofpain as bad as the individual can imagine, his or her maximum amount ofphantom limb pain typically felt over the past 24 hours. For patientswith both RLP and PLP, they were instructed to answer each question,i.e., they were instructed to record maximum daily pain levels in theirdiaries for both types of pain. Additionally or alternatively, patientsmay be instructed to record their average level of perceived pain overthe prior 24 hour period.

Results

Sufficient paresthesia coverage (average: >90%) andclinically-significant pain relief was obtained in 14 of the 16 (88%)amputees who completed the lead-placement visit. Of the 9 amputees whocompleted the 2-week home trial, the average improvements in the primaryoutcome measure (7-day mean worst pain intensity recorded in dailydiaries) was approximately 59% for RLP (n=6) and 60% for PLP (n=3) atthe end of treatment (EOT) relative to baseline. Many subjects continuedto experience pain relief after the leads were removed and stimulationwas turned off. At the last follow-up visit (4-wk post-EOT) the averageimprovement was approximately 66% for RLP and 52% for PLP. The resultsmay be seen in FIGS. 27-30 .

FIGS. 27 and 29 depict the average of the worst daily pain levels feltby the patients during the study for residual limb pain (RLP) andphantom limb pain (PLP), respectively. As can be seen in FIG. 27 , therewas up to a 5-point reduction in RLP during the treatment period (days0-14) and each patient had sustained RLP relief for at least four weeksafter the treatment ended. Thus, the RLP relief lasted at least twice aslong as the treatment method. As can be seen in FIG. 29 , there was upto a 4-point reduction in PLP during the treatment period (days 0-14)and each patient had sustained PLP relief for at least four weeks afterthe treatment ended. Thus, the PLP relief lasted at least twice as longas the treatment method. For the two patients that had both RLP and PLP(A-10, A-20), each had a relief of RLP by at least ninety percent at 4weeks past end of treatment and about 35 to about 75 percent relief ofPLP, as can be seen in FIGS. 28 and 30 , respectively.

Improvements were also reported in secondary outcome measures: PainInterference Scores of the Brief Pain Inventory-Short Form (EOT: 88%,4-wk post-EOT: 63%), the Pain Disability Index (EOT: 73%, 4-wk post EOT:67%), and the Beck Depression Inventory (EOT: 47%, 4-wk post-EOT: 61%).Improvements were also reported in the patient global impression ofchange (PGIC).

Case Series Conclusions

A method according to the present invention is the first to generateclinically-significant pain relief with a single-contact lead insertedpercutaneously to stimulate the large nerve trunks of the sciatic and/orfemoral nerves. The data also suggest the temporary percutaneous systemmay produce a significant carry-over effect that persists after EOT.

Perhaps more generally, what has been discovered is that placement of anelectrode at a therapeutically effective distance away from a nervebundle allows for selective recruitment of certain fibers within thebundle. Stated alternatively, an electrode spaced from a nerve widensthe therapeutic window for providing beneficial electrical stimulationto relieve pain. Conventional placement 910 of electrodes 912 forperipheral nerve stimulation can be seen in FIG. 31 . Electricalstimulation 914 is applied to a nerve bundle 916, such as a nerve trunkincluding multiple nerve fiber sizes and/or types, and is likely torecruit activation of both targeted fibers (such as Ia and Ib afferentfibers) and untargeted or undesirable nerve fibers (such as the otherfiber types illustrated therein; i.e., III, IV, etc.). FIG. depicts anelectrode placement 920 according to the present invention at sometherapeutically effective distance 922 away from the nerve bundle ortrunk 916, which includes all of the nerve fiber types (i.e., Type Ia,Ib, III, and IV), as well as their sizes relative to one another, asillustrated in FIG. 32

It is known that for activation of a neural fiber having a particularfiber diameter with an electrode placed at a predetermined distance fromthe fiber, the relationship between electrical stimulation amplitude andthe pulse duration of such stimulation is generally inverselylogarithmically proportional. However, across fiber diameters, therelationships are convergent, as can be seen in FIG. 33 . Conventionalperipheral nerve stimulation is usually provided at a stimulationamplitude of less than 2 mA (often about 0.2 mA to about 0.3 mA orless), so as to avoid causing pain or damage to the neural tissue,usually against which electrodes are positioned. At this stimulationamplitude level, it can be seen that conventional PNS 950 has a verynarrow window in which to operate before such stimulation leads torecruitment of activation of smaller, perhaps undesirable nerve fibers.However, if nerve fibers such as afferent nerve fibers having a diameterof about 20 μm are bundled at a stimulation location with other smallernerve fibers, such as efferent nerve fibers, methods according to thepresent invention expand the window of stimulation amplitude 960 so asto minimize the chances of recruiting activation of the undesirable,smaller nerve fibers. That is, using a method according to the presentinvention with an electrode spaced at 1 mm from a targeted nerve fiber,instead of being constrained to an amplitude of about 0.2 to about 0.3mA (e.g. providing a window of about 0.1 mA), an amplitude in the rangeof about 0.9 to about 1.6 mA may be used, thus expanding the acceptablestimulation variability up to seven fold (e.g. providing a window ofabout 0.7 mA). While modeled numbers have been used to demonstrate theconcept of a wider or less sensitive therapeutic window provided bymethods according to the present invention, it is to be understood thatthe exact extent of an increase in the therapeutic window as describedwill vary depending upon patient biological factors, electrodeproperties, nerve fiber composition, and clinician technique.

Likewise, for activation at a given electrode spacing from a neuralfiber, the relationship between stimulation current required foractivation of the fiber and the neural fiber diameter is generallyinversely logarithmically proportional given a fixed pulse duration orwidth. However, across electrode placement spacing distances, therelationships are convergent, as can be seen in FIG. 34 . As stated,conventional peripheral nerve stimulation is usually provided at astimulation amplitude of about 0.2 mA to about 0.3 mA, so as to avoidcausing pain or damage to the neural tissue, usually against whichelectrodes are positioned. At this stimulation amplitude level, it canbe seen that conventional PNS 970 has a very narrow window in which tooperate before such stimulation leads to recruitment of activation ofsmaller, perhaps undesirable nerve fibers. However, if nerve fibers suchas afferent nerve fibers having a diameter of about 20 μm are bundled ata stimulation location with other smaller nerve fibers, such as efferentnerve fibers or smaller afferent nerve fibers, methods according to thepresent invention expand the window of stimulation amplitude 980 so asto minimize the chances of recruiting activation of the undesirable,smaller nerve fibers. Thus, systems and methods according to the presentinvention provide one or more advantages, such as less risk of neuralinjury to a patient and greater or wider variability in stimulationdelivery.

IV. Conclusion

In “nerves of passage” stimulation, the lead is placed in tissue (e.g.muscle, adipose, connective, or other connective tissue) by which thetargeted nerve passes, but stimulation actually relieves pain that isfelt distal (downstream) from where the lead is placed. In “nerves ofpassage” stimulation, the lead can be placed in tissue (e.g. muscle,adipose, connective, or other tissue) that is conveniently located neara nerve trunk that passes by the lead on the way to the painful area.The key is that the lead is placed in tissue (e.g. muscle, adipose,connective, or other tissue) that is not the target (painful) muscle,but rather tissue (e.g. muscle, adipose, or other connective tissue)that is proximal (upstream) from the painful region because the proximaltissue (e.g. muscle, adipose, connective, or other tissue) is a moreconvenient and useful location to place the lead.

The advantages of nerves of passage stimulation can be recognized byanesthesiologists who are used to placing needles deeper in the tissue(e.g. muscle, adipose, connective, or other tissue) near nerves ofpassage Anesthesiologists are accustomed to placing needles proximal(upstream) from the areas of pain to numb the areas downstream.Anesthesiologists already use ultrasound and the electro-locationtechniques that would be needed to place leads to access nerves ofpassage.

Nerves of passage stimulation provides stimulation-generatedparesthesias (that ideally overlap with the area of pain) but does notrequire evoking a muscle contraction to place the lead correctly. Thetarget regions in which pain is felt and which are targeted forgeneration of paresthesia are not the same region in which the lead isplaced. This is an advantage because physicians (e.g. anesthesiologists,physiatrists, neurosurgeons, and/or other pain specialists) who willtypically be placing the lead are accustomed to using paresthesias(sensory feedback description of from the patient) to guide leadplacement and tuning of stimulation parameters.

Evoking muscle contraction with stimulation is not required for painrelief or lead location. Evoking muscle contraction with stimulation mayhelp in relieving pain or placing the lead, but it is not required. Itis an advantage that muscle contraction is not required because itallows this method to treat pains in which muscle contraction cannot beevoked (e.g. in the case of amputation pain in which the target area hasbeen amputated and is no longer physically present or other cases ofnerve damage either due to a degenerative diseases or conditions such asdiabetes of impaired vascular function, in which the nerves are slowlydegenerating, progressing from the periphery, or due to trauma.

In nerves of passage stimulation, the primary targeted pain area isdistal to the lead, meaning that the lead is in between the major areain which pain (e.g. the worst, most troubling, or most interfering pain)is felt and the center of the body (e.g. the spinal cord)).

Imaging (e.g., ultrasound or an alternate imaging technique, e.g.fluoroscopy) may be used to improve lead placement near nerves ofpassage. Ultrasound may improve lead placement in the form of increasingthe total speed of the procedure (shortening the procedure's duration,not necessarily increasing the speed at which the lead is advanced inthe form of locating the lead in a more optimal location (to improverecruitment of the target fibers in the target nerve and minimizerecruitment of non-target fibers (e.g. c fibers, other non-targetsensory fibers, motor fibers, etc.) in either the target nerve and/or innon-target nerve (s); in the form of minimizing risk and/or damage tothe patient during placement of the lead (by avoiding blood vessels,organs, bones, ligaments, tendons, lymphatic vessels, &/or otherstructures) that may be damaged. One reason that imaging may be usefulis that some nerves of passage are (but do not have to be) locatedrelatively deeply. Fluoroscopy is not required to place the lead. It mayhelp, but it is not required. Imaging is not required.

The patient is not required to give verbal, written, or other type offeedback or indication of what they feel as the lead is being advancedtowards the nerve of passage if muscle contraction or imaging is used toguide lead placement, but patient feedback during lead advancement mayimprove lead placement in some patients, especially in cases where(distal) muscle contraction cannot be used to confirm correct leadplacement (e.g. amputees, nerve injury, nerve degeneration (e.g. due tovascular dysfunction, diabetes, etc.), stimulation of a sensory nerve)The patient may indicate sensations during tuning of stimulus intensity(but this is a different step in the process and is performed after thelead has been correctly positioned). As non-limiting examples, thosesensations reported by the patient may include first sensation (minimumstimulus intensity that evokes a sensation), level of comfort, maximumtolerable sensation, pain, qualities &/or descriptions of thesensations.

The region in which the patient perceives stimulation-induced sensationsand/or paresthesias may be an important indicator of the potentialsuccess of the therapy (e.g. used in screening potential candidates),and the stimulation parameters (including but not limited to leadlocation) may be adjusted so that the region in which paresthesias areperceived overlaps with the region of pain.

As an alternative to using perception of stimulation induced sensationsand/or paresthesia, the level of pain and/or change in the intensity ofpain during and/or due to stimulation may be used to adjust stimulationparameters (including but not limited to lead location). The foregoingis considered as illustrative only of the principles of the invention.Furthermore, since numerous modifications and changes will readily occurto those skilled in the art, it is not desired to limit the invention tothe exact construction and operation shown and described. While thepreferred embodiment has been described, the details may be changedwithout departing from the invention, which is defined by the claims.

1. A stimulation system comprising: an open-coiled wire lead having athickness and a diameter configured for percutaneous insertion into aportion of a body; a plurality of electrodes each formed integrally onthe coiled wire lead, wherein the electrodes are spaced apart from oneanother with an insulated portion positioned between at least two of theplurality of electrodes; and an electrical stimulation deviceoperatively coupled to the coiled wire lead and configured to applyelectrical stimulation through the plurality of electrodes.
 2. Thestimulation system of claim 1, wherein the electrodes are configured tobe positioned in tissue a distance spaced from (i) at least one of aType Ia and Ib afferent nerve fibers and (ii) at least one of Type IIIand Type IV nerve fibers.
 3. The stimulation system of claim 2, whereinthe electrical stimulation selectively activates at least one of theType Ia and Ib afferent nerve fibers while minimizing recruitment ofactivation of the at least one of Type III and Type IV nerve fibersbecause the plurality of electrodes are spaced the distance from the atleast one of a Type Ia and Ib afferent nerve fibers and the at least oneof Type III and Type IV nerve fibers.
 4. The stimulation system of claim3, wherein the electrical stimulation device comprises an external pulsegenerator.
 5. A stimulation system comprising: a coiled wire leadconfigured for percutaneous insertion into a body, wherein the coiledwire lead comprises a plurality of electrodes each formed integrally onthe coiled wire lead, wherein the electrodes are spaced apart from oneanother with an insulated portion positioned between at least two of theplurality of electrodes; and an electrical stimulation deviceoperatively coupled with the coiled wire, wherein the electricalstimulation device is configured to deliver electrical stimulationthrough the plurality of electrodes to a neural fiber bundle within abody.
 6. The stimulation system of claim 5, wherein the plurality ofelectrodes are configured to be positioned in tissue in electricalproximity to but spaced away from the neural fiber bundle, wherein theneural fiber bundle comprises at least one of a Type Ia and Ib afferentnerve fiber and an efferent nerve fiber.
 7. The stimulation system ofclaim 6, wherein the at least one of Type Ia and Ib afferent nerve fiberof the neural fiber bundle are selectively activated while minimizingrecruitment of activation of the efferent nerve fiber of the neuralfiber bundle because the plurality of electrodes is in electricalproximity but spaced away from the neural fiber bundle to reduce aperception of pain.
 8. The stimulation system of claim 7, whereinselectively activating at least one of the Type Ia and Ib afferent nervefibers includes selectively activating both of the Type Ia and Ibafferent nerve fibers.
 9. The stimulation system of claim 7, whereinminimizing recruitment of activation includes minimizing recruitment ofactivation of at least one of a Type III and Type IV nerve fiber of theneural fiber bundle.
 10. The stimulation system of claim 7, whereinminimizing recruitment of activation includes minimizing recruitment ofactivation of both of Type III and Type IV nerve fibers of the neuralfiber bundle.
 11. The stimulation system of claim 7, wherein theelectrical proximity to but spaced away from the neural fiber bundlecomprises 0.5 to 3 cm from the neural fiber bundle.
 12. The stimulationsystem of claim 7, wherein the electrical stimulation device comprisesan external pulse generator.
 13. A stimulation system comprising: a leadcomprising at least two electrodes, wherein the at least two electrodesare spaced apart from one another with an insulated portion positionedbetween them and wherein one of the electrodes is configured to bepositioned at a therapeutically effective distance from a neural fiberbundle within tissue, wherein the neural fiber bundle comprises morethan one type of nerve fiber; and an electrical stimulation deviceoperatively coupled with the lead, the electrical stimulation deviceconfigured to deliver electrical stimulation from the electrodes to theneural fiber bundle.
 14. The stimulation system of claim 13, wherein alead connector connects the electrical stimulation device to the lead.15. The stimulation system of claim 13, wherein a first of the type ofnerve fiber is selectively activated while minimizing recruitment ofactivation of a second of the type of nerve fiber because the electrodesare at the therapeutically effective distance and wherein the electricalstimulation evokes paresthesia in a region of pain, wherein the regionof pain is spaced from the electrodes.
 16. The stimulation system ofclaim 15 further comprising an introducer needle, wherein the electrodesare placed using the introducer needle percutaneously inserted into thetissue.
 17. The stimulation system of claim 13, wherein the electricalstimulation device comprises an external pulse generator.
 18. Astimulation system comprising: a lead comprising at least twonon-insulated portions, wherein the at least two non-insulated portionare spaced apart from one another with an insulated portion positionedbetween them and wherein one of the at least two non-insulated portionsis configured to be positioned at a therapeutically effective distancefrom a neural fiber bundle within tissue, wherein the neural fiberbundle comprises more than one type of nerve fiber; and an electricalstimulation device operatively coupled with the lead, the electricalstimulation device configured to deliver electrical stimulation to theneural fiber bundle.
 19. The stimulation system of claim 18, wherein theone of the at least two non-insulated portions is an electrode throughwhich the electrical stimulation is delivered.
 20. The stimulationsystem of claim 19, wherein the electrical stimulation device is fixedto the lead.
 21. The stimulation system of claim 19, further comprisinga surface electrode operatively coupled with the electrical stimulationdevice.
 22. The stimulation system of claim 21, wherein the surfaceelectrode serves as an anode.
 23. The stimulation system of claim 21,wherein the surface electrode serves as a cathode.
 24. The stimulationsystem of claim 18, wherein the lead comprises a coiled lead with one ormore coiled metal wires with in an open core and is insulated and coatedwith a material stabilizing the lead.
 25. The stimulation system ofclaim 24, wherein the insulation comprises a biocompatible film.
 26. Thestimulation system of claim 24, wherein the insulation comprises abiocompatible polymer film.
 27. The stimulation system of claim 19,wherein the electrical stimulation delivered by the electricalstimulation device is configured to be scaled to account for variationsin a geometry of the electrode.
 28. The stimulation system of claim 19,wherein the electrical stimulation device is configured to account forvariations in current density resulting from variations in a geometry ofthe electrode.
 29. The stimulation system of claim 19, wherein theelectrode comprises a spherical, raised, and depressed characteristicsand contours that are undulating.
 30. The stimulation system of claim19, wherein the electrode comprises hemispherical, raised, and depressedcharacteristics and contours that are undulating.
 31. The stimulationsystem of claim 19, wherein the electrode comprises elevated andrecessed characteristics and contours that are continuous andundulating.
 32. The stimulation system of claim 19, wherein electrodecomprises a contact configuration that is intermittent.
 33. Thestimulation system of claim 19, wherein the electrode is spherical. 34.The stimulation system of claim 19, wherein the lead is configured towithstand mechanical forces and resist migration during a home trial.35. The stimulation system of claim 34, wherein the home trial lasts fortwo weeks.